Cell Cycle

ROCK Inhibitors as an Alternative Therapy for Corneal Grafting: A Systematic Review

329 | Feb 15 2024

The review on ROCK inhibitors for corneal wound healing showcases their diverse therapeutic potential across various ocular conditions, offering promise as an effective alternative to human donor tissue for addressing the significant unmet medical need in corneal blindness. [Read the Full Post]

Proteomic and Phosphoproteomic Profiling Reveals the Oncogenic Role of Protein Kinase D Family Kinases in Cholangiocarcinoma

281 | Feb 15 2024

The comprehensive analysis of protein and phosphorylation signatures in cholangiocarcinoma revealed the PRKD family's pivotal role, highlighting their potential as novel treatment targets validated by the inhibitory effects of 1-naphthyl PP1 on CCA cell proliferation, migration, and invasion. [Read the Full Post]

Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II

75 | Feb 14 2024

The study's identification of a genomic modification in Ids-deficient mice underscores a possible connection between IDS deficiency and the augmented differentiation of calvarial bone, shedding light on the enlarged head circumference observed in individuals affected by MPS II. [Read the Full Post]

Hypoxia-activated glutamine antagonist prodrug combined with combretastatin A4 nanoparticles for tumor-selective metabolic blockade

93 | Feb 13 2024

The development of HDON, a hypoxia-activated prodrug derived from DON, coupled with combretastatin A4 nanoparticles, demonstrates exceptional tumor selectivity and efficacy, achieving remarkable tumor suppression rates and cure rates in murine liver, colon, and breast cancer models. [Read the Full Post]

Enhancing or Quenching of a Mitochondria-Targeted AIEgens-Floxuridine Sensor by the Regulation of pH-Dependent Self-assembly, Efficient Recognition of Hg2+, and Stimulated Response of GSH

134 | Feb 03 2024

The versatile TPE-FdU fluorescent probe, exhibiting pH-responsive behavior, selective Hg2+ ion detection, and intracellular mitochondrial visualization, represents a promising advancement with diverse applications in cell imaging, environmental monitoring, and biomedical research. [Read the Full Post]

Polo-like kinase 4 inhibitor CFI-400945 inhibits carotid arterial neointima formation but increases atherosclerosis

54 | Jan 31 2024

CFI-400945 demonstrates dual effects by inhibiting neointima formation while accelerating atherosclerosis, attributed to its induction of mitotic arrest, polyploidization, and apoptosis in smooth muscle cells. [Read the Full Post]

Y box binding protein 1 inhibition as a targeted therapy for ovarian cancer

74 | Jan 30 2024

The discovery of SU056, a potent YB-1 inhibitor exhibiting multifaceted impacts on ovarian cancer progression, apoptosis promotion, and synergy with paclitaxel while reducing treatment-associated toxicities, suggests a promising strategy for combating tumor growth and treatment resistance. [Read the Full Post]

Assessing safety concerns of interstitial lung disease associated with antibody-drug conjugates: a real-world pharmacovigilance evaluation of the FDA adverse event reporting system

179 | Jan 29 2024

The identification of significant safety signals for interstitial lung disease associated with several FDA-approved antibody-drug conjugates underscores the critical need for heightened clinician awareness and early patient monitoring, prompting further research and potential adjustments in clinical practice guidelines. [Read the Full Post]

Axillary Nodal Response to Neoadjuvant T-DM1 Combined with Pertuzumab in a Prospective Phase II Multi-Institution Clinical Trial

155 | Jan 29 2024

In HER2-positive breast cancer patients undergoing neoadjuvant dual HER2-targeted therapy, achieving a pathologic complete response or residual cancer burden I in the breast strongly correlates with a high probability of having no residual disease in the axillary lymph nodes, suggesting a potential consideration for omitting axillary surgical staging in future trials for those demonstrating these favorable responses. [Read the Full Post]

Lysosomes, caspase-mediated apoptosis, and cytoplasmic activation of P21, but not cell senescence, participate in a redundant fashion in embryonic morphogenetic cell death

60 | Jan 27 2024

This study employing micromass cultures reveals a complex interplay of apoptotic events and cellular changes during tissue remodeling, challenging the conventional association of SA-β-Gal positivity with cell senescence in developmental processes. [Read the Full Post]

Antitumor effect of a small-molecule inhibitor of KRASG12D in xenograft models of mucinous appendicular neoplasms

107 | Jan 25 2024

The profound inhibition of tumor growth in a high-grade PMP xenograft mouse model carrying a KRASG12D mutation by the small-molecule KRASG12D inhibitor MRTX1133 underscores its potent efficacy and supports its potential for clinical translation in treating PMP. [Read the Full Post]

RGCC-mediated PLK1 activity drives breast cancer lung metastasis by phosphorylating AMPKα2 to activate oxidative phosphorylation and fatty acid oxidation

67 | Jan 25 2024

The study reveals that RGCC overexpression drives a signaling cascade, involving PLK1 and AMPKα2, enhancing metabolic adaptations in TNBC cells, providing crucial insights and potential therapeutic targets for combating lung-specific metastasis in triple-negative breast cancer. [Read the Full Post]

Clinical development of WEE1 inhibitors in gynecological cancers: A systematic review

63 | Jan 24 2024

This systematic review consolidates evidence showcasing the promising efficacy of WEE1 inhibitors in gynecological malignancies while highlighting the significance of biomarker-driven patient selection for optimizing treatment response. [Read the Full Post]

CRISPR screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer

112 | Jan 23 2024

The study uncovers that while KRASG12C inhibitors initially exhibit promising responses, combining them with SHP2, PI3K, and CDK4/6 inhibitors extends regression in preclinical models, yet resistance emerges via KRASG12C amplification and MAPK/PI3K pathway alterations, with FGFR1 loss sensitizing and PTEN loss rescuing against the KRASG12C/SHP2 inhibition. [Read the Full Post]

Covid-19 co-infection with Crimean Congo haemorrhagic fever (CCHF) in a CCHF endemic country: a case report

121 | Jan 22 2024

In regions where both Crimean-Congo hemorrhagic fever and severe COVID-19 coexist, differentiating between the two diseases is vital due to their overlapping clinical presentations, emphasizing the importance of accurate diagnostic testing to guide appropriate treatment strategies. [Read the Full Post]

Fanconi anemia repair pathway dysfunction, a potential therapeutic target in lung cancer

51 | Jan 21 2024

Identifying DNA repair deficiencies in lung cancer through the FATSI method may pave the way for tailored treatments targeting specific vulnerabilities, potentially revolutionizing therapeutic strategies for a subset of patients. [Read the Full Post]

Inhibitors of One or More Cellular Aurora Kinases Impair the Replication of Herpes Simplex Virus 1 and Other DNA and RNA Viruses with Diverse Genomes and Life Cycles

0 | Jan 10 2024

The discovery of aurora kinase inhibitors significantly impairing HSV-1 gene expression and replication, while also impacting other viral families, illuminates a promising avenue for broad-spectrum antiviral therapies targeting these pivotal cellular kinases. [Read the Full Post]

Targeting the survival kinase DYRK1B: A novel approach to overcome radiotherapy-related treatment resistance

64 | Jan 09 2024

Targeting the stress-enhanced survival kinase DYRK1B alongside irradiation demonstrates a synergistic effect in eliminating colorectal tumor cells under harsh environmental stressors, offering a promising strategy to overcome treatment resistance. [Read the Full Post]

Target-based virtual screening, computational multiscoring docking and molecular dynamics simulation of small molecules as promising drug candidate affecting kinesin-like protein KIFC1

69 | Jan 09 2024

The computational analysis identified mcule-4895338547 as a promising small-molecule inhibitor targeting KIFC1, showing strong binding affinity and favorable properties, holding potential for further exploration in cancer treatment. [Read the Full Post]

Active natural compounds perturb the melanoma risk-gene network

179 | Jan 07 2024

The study ingeniously employs network modeling of melanoma-associated genes, revealing crucial pathways and potential therapeutic targets while showcasing the predictive potential of this model in evaluating the efficacy of anti-melanoma phytochemicals. [Read the Full Post]

Runx3 Restoration Regresses K-Ras-Activated Mouse Lung Cancers and Inhibits Recurrence

124 | Jan 02 2024

The study's findings suggest that the restoration of RUNX3 presents a promising therapeutic avenue for effectively treating K-RAS-activated lung cancers by regressing tumors and suppressing recurrence through multifaceted pathways, potentially offering a durable response. [Read the Full Post]

Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments

0 | Dec 30 2023

Research into selective CDK9 inhibitors and PROTAC degraders shows promise in targeting specific tumor genotypes, with VIP152 demonstrating efficacy in advanced high-grade lymphoma and solid tumors, highlighting the potential for precision cancer therapy. [Read the Full Post]

CCT251545 enhances drug delivery and potentiates chemotherapy in multidrug-resistant cancers by Rac1-mediated macropinocytosis

101 | Dec 30 2023

The study's findings suggest that CCT251545 in combination with chemotherapy demonstrates a potent synergistic effect by enhancing drug uptake through Rac1-dependent macropinocytosis and elevating NAD levels, providing a promising avenue for managing multidrug-resistant cancers. [Read the Full Post]

Potential role of Acanthamoeba Rab7

123 | Dec 26 2023

The study elucidates the pivotal role of AcRab7 in Acanthamoeba castellanii's phagocytosis, endosomal delivery, and cellular physiology, demonstrating its influence on energy production, cell proliferation, and potential implications for understanding related parasitic diseases. [Read the Full Post]

Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats

101 | Dec 25 2023

This study on plinabulin's pharmacokinetics in rats suggests no significant differences between leukopenia and control groups, indicating its potential as a candidate for treating chemotherapy-induced leukopenia pending further human clinical trials. [Read the Full Post]

Degradation of Cyclin-Dependent Kinase 9/Cyclin T1 by Optimized Microtubule-Associated Protein 1 Light Chain 3 Beta-Recruiting Coumarin Analogs

119 | Dec 24 2023

Researchers systematically optimized coumarin analogs linked with the CDK9 inhibitor SNS-032, potentially enabling simultaneous binding to CDK9 and LC3B, initiating selective autophagic degradation and demonstrating potential for treating diseases associated with intracellular pathogenic proteins. [Read the Full Post]

AZD5438 a GSK-3a/b and CDK inhibitor is antiapoptotic modulates mitochondrial activity and protects human neurons from mitochondrial toxins

0 | Dec 23 2023

AZD5438, inhibiting CDKs and GSK-3a/b, emerges as a promising compound, showcasing potent neuroprotective effects by preventing mitochondrial dysfunction and neuronal damage induced by rotenone in human neurons, suggesting its potential therapeutic significance. [Read the Full Post]

Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma

120 | Dec 22 2023

This study employs a bioinformatics screening protocol integrating drug-sensitivity data and basal gene expression to predict synergistic combinations of histone deacetylase inhibitors (HDACi), identifying the sphingolipid signaling pathway as a promising target; further experimental validation reveals novel synergisms between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, as well as between HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod in the treatment of pancreatic ductal adenocarcinoma (PDAC). [Read the Full Post]

Predictive model for treatment outcomes of peripheral T-cell lymphoma, not otherwise specified, in Taiwanese patients

156 | Dec 20 2023

In this retrospective study of 104 peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) patients in Taiwan, the investigation revealed a poor prognosis, highlighted the potential efficacy of pralatrexate as salvage chemotherapy for eligible patients, identified adverse prognostic factors, and proposed a novel predictive index with distinct risk groups, emphasizing the need for further validation and exploration of improved treatment strategies. [Read the Full Post]

YBX1-interacting small RNAs and RUNX2 can be blocked in primary bone cancer using CADD522

89 | Dec 20 2023

The study reveals that transfer RNA-derived small RNAs, specifically tRF-GlyTCC, function as a constitutive tumor suppressor mechanism in primary bone cancer, attenuating pro-metastatic protein-RNA interactions by targeting RUNX2 via a shared sequence motif with YBX1, leading to the development of the therapeutic agent CADD522 with significant efficacy in reducing tumor progression and metastasis in PBC. [Read the Full Post]

Enhancing reporting quality and impact of early phase dose-finding clinical trials: CONSORT Dose-finding Extension (CONSORT-DEFINE) guidance

74 | Dec 18 2023

CONSORT-DEFINE provides international, consensus-driven guidelines for reporting early phase dose-finding trials, emphasizing essential items to enhance transparency, completeness, and reproducibility, thereby promoting clear interpretation and informed decision-making in medical research and practice. [Read the Full Post]

GRP78 acts as a cAMP/PKA signaling modulator through the MC4R pathway in porcine embryonic development

122 | Dec 17 2023

In this study, inhibiting Glucose-regulated protein 78 (GRP78) function using HA15 during porcine embryonic development disrupted the MC4R pathway, downregulated cAMP/PKA signaling, inhibited cell cycle progression, and induced mitochondrial dysfunction, revealing the crucial role of GRP78 in regulating these processes. [Read the Full Post]

Drug repurposing and structure-based discovery of new PDE4 and PDE5 inhibitors

62 | Dec 17 2023

The study utilized high-throughput drug repurposing screening and structure-based drug design to identify novel PDE4 inhibitors, leading to the unexpected discovery of a dual PDE4/PDE5 inhibitor (CVT-313) and the subsequent development of a highly selective PDE5 inhibitor (compound 2), exemplifying the efficiency of this integrated approach in drug discovery. [Read the Full Post]

Rac and Cdc42 inhibitors reduce macrophage function in breast cancer preclinical models

46 | Dec 16 2023

Rac and Cdc42 inhibitors EHop-016 and MBQ-167 demonstrate dual efficacy by simultaneously targeting metastatic cancer cells and immunosuppressive myeloid cells in the tumor microenvironment, creating an anti-tumor environment in breast cancer. [Read the Full Post]

5-HT6 receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines

124 | Dec 16 2023

The study presents a novel series of 6-piperazinyl-7-azaindoles demonstrating potent 5-HT6 receptor antagonism, with a focus on optimizing the lead structure and exploring structure-activity relationships, highlighting Compound 29 as a promising candidate for further drug development. [Read the Full Post]

Aberrant PI3Kδ splice isoform as a potential biomarker and novel therapeutic target for endocrine cancers

77 | Dec 15 2023

**Utilizing PI3Kδ-S as a Prognostic Biomarker and Therapeutic Target Offers a Promising Strategy for Advanced Endocrine Cancers.** [Read the Full Post]

Therapeutical interference with the epigenetic landscape of germ cell tumors: a comparative drug study and new mechanistical insights

99 | Dec 15 2023

The study identified seven epigenetic inhibitors that efficiently decreased cell viability in cisplatin-resistant Type II germ cell tumors, highlighting their potential as alternative therapeutic options, and provided comprehensive insights into their off-target effects and modes of action. [Read the Full Post]

Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3RT618I-driven cells

126 | Dec 14 2023

The study demonstrates that aurora kinase inhibitors, particularly reversine, exert significant antineoplastic effects in Ba/F3 cells expressing the CSF3RT618I mutation, reducing cell viability, clonogenicity, and proliferative capacity, while modulating key molecular pathways associated with cell cycle and apoptosis in the context of chronic neutrophilic leukemia (CNL). [Read the Full Post]

GPER1 contributes to T3-induced osteogenesis by mediating glycolysis in osteoblast precursors

74 | Dec 13 2023

T3 promotes osteogenesis in MC3T3-E1 cells by enhancing GPER1-mediated glycolysis, as evidenced by increased osteogenic activities, which are reversed by GPER1 inhibition and glycolysis blockade. [Read the Full Post]

Exosomal EIF5A derived from Lewis lung carcinoma induced adipocyte wasting in cancer cachexia

172 | Dec 11 2023

The study reveals that exosomal EIF5A derived from Lewis lung carcinoma cells induces adipocyte lipolysis in cancer cachexia by binding with GPBAR1 mRNA, activating the CREB signaling pathway, implicating EIF5A as a potential therapeutic target. [Read the Full Post]

Cyclin-dependent kinase 6 (CDK6) as a potent regulator of the ovarian primordial-to-primary follicle transition

73 | Dec 11 2023

The study reveals that CDK6 inhibition using BSJ disrupts the primordial-to-primary follicle transition, emphasizing the crucial role of precise cell cycle regulation in ovarian follicle development and suggesting potential implications for fertility-related interventions. [Read the Full Post]

Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core

41 | Dec 10 2023

In this study, a novel class of dihydroquinolines was developed, exhibiting potent inhibitory activities in the nanomolar range against DYRK1A and CLK1, two kinases implicated in Alzheimer's disease and Down syndrome, with the most potent inhibitor also demonstrating antioxidant and radical scavenging properties. [Read the Full Post]

A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems

47 | Dec 09 2023

Harnessing live-cell bright-field imaging and machine learning, this study enables real-time recognition of diverse cell types, predictive assessment of differentiation efficiency, and iterative optimization of pluripotent stem cell differentiation, ensuring consistent high efficiency across cell lines and batches for biomedical applications. [Read the Full Post]

TLR4 activation induces inflammatory vascular permeability via Dock1 targeting and NOX4 upregulation

74 | Dec 08 2023

The study demonstrates that the TLR4 inflammatory cascade disrupts vascular integrity by downregulating Dock1 and Elmo1 expression, highlighting Dock1 as a critical target in TLR4-mediated inflammatory lung injury and emphasizing its essential role in maintaining endothelial cell junctional integrity. [Read the Full Post]

Transcriptomics-Guided In Silico Drug Repurposing: Identifying New Candidates with Dual-Stage Antiplasmodial Activity

128 | Dec 08 2023

The research effort identified two promising compounds, HSP-990 and silvestrol aglycone, demonstrating potent inhibitory activity at nanomolar concentrations against the asexual blood stage of Plasmodium falciparum, with silvestrol aglycone showing low cytotoxicity and transmission-blocking potential, indicating their potential as dual-acting antimalarial and transmission-blocking candidates for malaria control. [Read the Full Post]

PFKFB3 Increases IL-1 β and TNF- α in Intestinal Epithelial Cells to Promote Tumorigenesis in Colitis-Associated Colorectal Cancer

73 | Dec 07 2023

Elevated expression of PFKFB3 in colitis-associated colorectal cancer promotes tumorigenesis by inducing phospho-p65 and the expression of pro-inflammatory cytokines IL-1β and TNF-α, highlighting PFKFB3 as a potential therapeutic target. [Read the Full Post]

Hepatic arterial infusion chemotherapy with or without lenvatinib for unresectable cholangiocarcinoma: a single-center retrospective study

99 | Dec 05 2023

**Combining FOLFOX hepatic arterial infusion chemotherapy with lenvatinib significantly prolongs overall and progression-free survival, making it a promising and safe treatment option for patients with unresectable cholangiocarcinoma.** [Read the Full Post]

ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42

34 | Dec 03 2023

The study reveals that ARHGEF37 upregulation in hepatocellular carcinoma promotes pulmonary metastasis by enhancing tumor cell adhesion to endothelial cells and trans-endothelial migration via direct activation of Cdc42, and targeted inhibition of this pathway using ZCL278 presents a potential therapeutic approach for preventing and treating HCC lung metastasis. [Read the Full Post]

Discovery of 4-(((4-(5-chloro-2-(((1s,4s)-4-((2-methoxyethyl)amino)cyclohexyl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile (JSH-150) as a novel highly selective and potent CDK9 kinase inhibitor

39 | Dec 02 2023

Compound 40 (JSH-150) is a highly selective CDK9 kinase inhibitor with an IC50 of 1 nM, demonstrating potent antiproliferative effects across multiple cancer cell lines, robust in vivo efficacy, and a promising pharmacological tool and drug candidate for leukemia and other cancers. [Read the Full Post]

Inverse Impact of Cancer Drugs on Circular and Linear RNAs in Breast Cancer Cell Lines

79 | Nov 30 2023

The study investigated the dysregulation of cancer-related circular RNAs (circRNAs) and their linear transcripts (linRNAs) in breast cancer cell lines exposed to various anticancer drugs, revealing altered circRNA/linRNA expression ratios and identifying specific circRNAs associated with apoptosis, cell migration, and mutated pathways, thereby shedding light on their potential roles as biomarkers and therapeutic targets in breast cancer treatment. [Read the Full Post]

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis

108 | Nov 29 2023

The study demonstrates that lauric acid induces eryptosis, a programmed cell death in red blood cells, and disrupts leukocyte distribution, providing key insights into its role in cardiovascular diseases and informing dietary interventions for prevention and management. [Read the Full Post]

Imidazole-4-N-acetamide Derivatives as a Novel Scaffold for Selective Targeting of Cyclin Dependent Kinases

57 | Nov 28 2023

The study explored imidazole-4-N-acetamide substituted derivatives of the pan-CDK inhibitor PHA-793887 and demonstrated a strong correlation between calculated binding parameters using non-equilibrium thermodynamics and inhibitory potencies in in vitro kinase assays, highlighting the method's effectiveness in predicting the activity of potential anticancer drug candidates. [Read the Full Post]

BMS-265246, a Cyclin-Dependent Kinase Inhibitor, Inhibits the Infection of Herpes Simplex Virus Type 1

31 | Nov 28 2023

BMS-265246 (BMS), a cyclin-dependent kinase (CDK) 1/2 inhibitor, has been identified as a potent anti-HSV-1 agent, effectively limiting viral multiplication in various cell lines and interfering with multiple stages of the HSV-1 replication process. [Read the Full Post]

Cytoplasmic Hsp70s promote EcR transport into the nucleus by responding to various stimuli

140 | Nov 27 2023

This study reveals that cytoplasmic Hsp70s facilitate the transport of the ecdysone receptor (EcR) into the nucleus in response to diverse stimuli, shedding light on the intricate mechanisms underlying insect metamorphosis and highlighting potential applications in pest control and broader biological research. [Read the Full Post]

Indole derivatives targeting colchicine binding site as potential anticancer agents

74 | Nov 27 2023

Research on indole derivatives targeting the colchicine-binding site (CBS) of microtubules holds significant promise for the development of novel and effective anticancer therapies with improved efficacy and reduced toxicity. [Read the Full Post]

Overfit deep neural network for predicting drug-target interactions

267 | Nov 27 2023

The OverfitDTI framework utilizes intentionally overfitted deep neural networks to accurately capture the intricate relationships between drugs and targets, enabling precise drug-target interaction predictions, as demonstrated by the successful identification and experimental validation of TEK inhibitors. [Read the Full Post]

TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma

75 | Nov 26 2023

Inhibition of TTK Protein Kinase (TTK) using specific inhibitors, in combination with Temozolomide (TMZ) chemotherapy, overcomes TMZ resistance in glioblastoma multiforme (GBM) cells by suppressing autophagy, suggesting a promising therapeutic strategy for improving treatment outcomes in GBM patients. [Read the Full Post]

DOCK2 is involved in the host genetics and biology of severe COVID-19

81 | Nov 24 2023

A genome-wide association study in a Japanese population identified a specific genetic variant (rs60200309-A) near the DOCK2 gene on chromosome 5, linked to decreased DOCK2 expression in immune cells, revealing its crucial role in the host immune response to SARS-CoV-2 infection and suggesting its potential as a biomarker and therapeutic target for severe COVID-19. [Read the Full Post]

HDAC11 mediates the ubiquitin-dependent degradation of p53 and inhibits the anti-leukemia effect of PD0166285

63 | Nov 23 2023

The study demonstrates the potential of the WEE1 inhibitor PD0166285 as a promising chemotherapeutic drug for acute myeloid leukemia, highlighting the negative correlation between HDAC11 expression and AML patient survival, and revealing HDAC11's impact on p53 stability and MAPK pathway phosphorylation levels. [Read the Full Post]

Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity

86 | Nov 22 2023

The study reveals that TTK inhibitors, particularly those inducing a shift in the glycine-rich loop by binding to the catalytic lysine at position 553, disrupt the catalytic machinery, leading to potent anti-proliferative effects, offering promising avenues for cancer treatment. [Read the Full Post]

High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers

92 | Nov 22 2023

BOS172722 is a potent spindle assembly checkpoint kinase MPS1 inhibitor that, in combination with paclitaxel, demonstrates significant synergistic effects, inducing chromosomal segregation defects and robust tumor regressions in preclinical models of triple-negative breast cancer, indicating its potential as a promising therapeutic approach for this patient population. [Read the Full Post]

Identifying promising GSK3β inhibitors for cancer management: a computational pipeline combining virtual screening and molecular dynamics simulations

126 | Nov 21 2023

The computational screening study identified BMS-754807 and GSK429286A as promising GSK3β inhibitors with high binding affinities, suggesting their potential as novel anticancer drugs pending experimental validation. [Read the Full Post]

Identification of circRNA-miRNA-mRNA network regulated by Hsp90 in human melanoma A375 cells

122 | Nov 21 2023

The study reveals that targeting the ECM-receptor interaction pathway, specifically the integrin (ITG) and collagen (COL) network, following Hsp90 inhibition by SNX-2112, offers a promising and novel therapeutic approach for melanoma treatment. [Read the Full Post]

Heat shock factor 1 is a promising therapeutic target against adult T-cell leukemia

155 | Nov 18 2023

Targeting the overexpressed heat shock factor 1 (HSF1) with the inhibitor KRIBB11 inhibits proliferation, induces apoptosis, disrupts essential signaling pathways, and sensitizes adult T-cell leukemia cells to HSP90 inhibition, offering a potential therapeutic approach for ATL. [Read the Full Post]

Drug Repurposing Analysis for Colorectal Cancer through Network Medicine Framework: Novel Candidate Drugs and Small Molecules

82 | Nov 18 2023

The study identified a novel gene module associated with colorectal cancer and proposed several previously studied (including polyethylene glycol, pantoprazole, trametinib) and novel (such as lornoxicam, suxamethonium, HDAC6 inhibitor ISOX) drug-repurposing candidates based on network biology approaches and differential co-expression analysis. [Read the Full Post]

The Novel, Orally Bioavailable CDK9 Inhibitor Atuveciclib Sensitises Pancreatic Cancer Cells to TRAIL-induced Cell Death

64 | Nov 16 2023

This study demonstrates that the combination of Atuveciclib and TRAIL effectively reduces the viability of pancreatic ductal adenocarcinoma (PDAC) cells, inducing apoptosis and cell-cycle arrest, thus suggesting its potential as a promising therapeutic strategy for PDAC treatment, including resistant and patient-derived xenograft (PDX) cell lines. [Read the Full Post]

PHA-680626 Is an Effective Inhibitor of the Interaction between Aurora-A and N-Myc

78 | Nov 16 2023

The study identifies PHA-680626 as a dual-function inhibitor capable of disrupting the AURKA/N-Myc interaction, offering a promising therapeutic strategy for treating neuroblastoma by destabilizing this oncogenic complex. [Read the Full Post]

Pin1 inhibitor API-1 sensitizes BRAF-mutant thyroid cancers to BRAF inhibitors by attenuating HER3-mediated feedback activation of MAPK/ERK and PI3K/AKT pathways

86 | Nov 15 2023

The study demonstrates that the Pin1 inhibitor API-1 enhances the sensitivity of BRAF-mutant thyroid cancer cells to the BRAF inhibitor PLX4032 by blocking the reactivation of MAPK/ERK and PI3K/AKT pathways via downregulation of HER3, offering a promising combination therapy for this cancer type. [Read the Full Post]

Multi-omics analysis reveals the association between elevated KIF18B expression and unfavorable prognosis, immune evasion, and regulatory T cell activation in nasopharyngeal carcinoma

91 | Nov 15 2023

Kinesin Family Member 18B (KIF18B) overexpression in Nasopharyngeal Carcinoma (NPC) is associated with poor prognosis, immune suppression, epithelial-mesenchymal transition (EMT), N6-methyladenosine (m6A) modification, and resistance to both immunotherapy and chemotherapy, making it a significant prognostic marker with potential therapeutic implications. [Read the Full Post]

IL-17 Is a Key Regulator of Mucin-Galectin-3 Interactions in Asthma

100 | Nov 15 2023

Galectin-3 (Gal-3) appears to play a pivotal role in the pathogenesis of asthma by regulating airway inflammation and mucin gene expression, suggesting that targeting Gal-3 could be a promising therapeutic strategy for the disease. [Read the Full Post]

AZD5438 a GSK-3a/b and CDK inhibitor is antiapoptotic modulates mitochondrial activity and protects human neurons from mitochondrial toxins

60 | Nov 14 2023

The study suggests that AZD5438, a compound targeting GSK-3a/b and CDKs, holds significant therapeutic potential due to its ability to prevent mitochondrial dysfunction, promote neuroprotection, and enhance glycolytic respiration, particularly in neuronal cells. [Read the Full Post]

HSP70 attenuates neuronal necroptosis through the HSP90α-RIPK3 pathway following neuronal trauma

141 | Nov 14 2023

Activation of HSP70 protects against necroptosis in neuronal trauma, with HSP90α-mediated regulation of RIPK3 and MLKL contributing to this protective effect. [Read the Full Post]

Segmental Zoster Paresis Accompanied by Horner's Syndrome

220 | Nov 11 2023

In this case, a 90-year-old immunocompromised woman developed right upper limb weakness and Horner's syndrome following oral therapy for zoster on the right T2 dermatome, with aggressive intravenous treatment leading to improvement in the former but persistence of the latter. [Read the Full Post]

Physalis Mottle Virus-Like Nanocarriers with Expanded Internal Loading Capacity

78 | Nov 10 2023

The engineering of cysteine-added mutants of PhMV VLPs has significantly improved their reactivity and cargo-loading capacity, making them promising nanocarriers for precise delivery of small-molecule drugs and imaging reagents in vivo. [Read the Full Post]

Inhibition of CDC20 potentiates anti-tumor immunity through facilitating GSDME-mediated pyroptosis in prostate cancer

90 | Nov 10 2023

The study reveals that CDC20 negatively regulates pyroptosis by targeting GSDME for ubiquitin-mediated proteolysis in prostate cancer, and its inhibition enhances anti-tumor immunity and synergizes with anti-PD1-based immunotherapy, offering novel therapeutic avenues for this cancer type. [Read the Full Post]

Combined inhibition of aurora kinases and Bcl-xL induces apoptosis through select BH3-only proteins

222 | Nov 08 2023

The study demonstrates that combining small-molecule inhibitors of AURK with BH3-mimetic inhibitors targeting Bcl-xL potently induces apoptosis and may overcome resistance to AURK inhibitors in colon cancer cells. [Read the Full Post]

Efficacy and safety of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of esophageal squamous cell cancer: A prospective, open label, randomized phase II study

102 | Nov 08 2023

The combination of irinotecan and raltitrexed may lead to better progression-free survival and overall survival compared to irinotecan monotherapy, especially in the second-line treatment of metastatic esophageal squamous cell cancer. [Read the Full Post]

Identification of inhibitors for the transmembrane Trypanosoma cruzi eIF2α kinase relevant for parasite proliferation

39 | Nov 08 2023

The study demonstrates that the TcK2 protein kinase in Trypanosoma cruzi plays a crucial role in parasite proliferation and differentiation, and Dasatinib shows potential as a lead inhibitor for developing therapeutics targeting TcK2 in the treatment of Chagas disease. [Read the Full Post]

Epigenetic regulator BMI1 promotes alveolar rhabdomyosarcoma proliferation and constitutes a novel therapeutic target

73 | Nov 05 2023

This study suggests that targeting BMI1, an epigenetic regulator, may offer a potential therapeutic strategy for alveolar rhabdomyosarcoma (ARMS) by inhibiting cell growth, promoting apoptosis, and activating the Hippo pathway. [Read the Full Post]

GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage

96 | Nov 04 2023

The study demonstrated that the small molecule inhibitor YUM70, which targets the GRP78 protein, effectively blocked SARS-CoV-2 viral entry and infection in vitro and in vivo, suggesting its potential as a promising therapeutic approach against COVID-19 and its variants. [Read the Full Post]

CX3CL1 in the red bone marrow promotes renal cell carcinoma to metastasize to the spine by involving the Src-related pathway

119 | Oct 30 2023

CX3CL1 promotes migration and invasion of renal cell carcinoma (RCC) cells, potentially facilitating RCC metastasis to the spine, through activation of the Src/FAK signaling pathway. [Read the Full Post]

Identification of novel inhibitors for trigger factor (TF) of M. tb: an in silico investigation

80 | Oct 29 2023

A computational model of the Mycobacterium tuberculosis trigger factor protein was developed and two potential inhibitors, HTS02984 and S06856, were identified through virtual screening, offering potential avenues for the development of tuberculosis therapies. [Read the Full Post]

Identification of Tau-Tubulin Kinase 1 Inhibitors by Microfluidics-based Mobility Shift Assay from a Kinase Inhibitor Library

156 | Oct 29 2023

This study identified a peptide substrate for human TTBK1 and developed a microfluidics-based assay, enabling the screening of kinase inhibitors and the potential development of novel hTTBK1 inhibitors for Alzheimer's disease prevention. [Read the Full Post]

Dbf4-Cdc7 (DDK) Inhibitor PHA-767491 Displays Potent Anti-Proliferative Effects via Crosstalk with the CDK2-RB-E2F Pathway

50 | Oct 28 2023

The study reveals that PHA-767491, through its potent inhibition of DDK and the CDK2-Rb-E2F transcriptional network, exhibits increased anti-proliferative effects in RB+ cancer cell lines by targeting the initiation phase of DNA replication and reducing the transcription of G1/S regulators. [Read the Full Post]

Ribonucleotide reductase regulatory subunit M2 drives glioblastoma TMZ resistance through modulation of dNTP production

132 | Oct 26 2023

In this study, the increased expression of ribonucleotide reductase regulatory subunit M2 (RRM2) and its regulation of dGTP and dCTP production during temozolomide (TMZ) therapy were identified as key factors in driving chemoresistance in glioblastoma (GBM), and treatment with the RRM2 inhibitor 3-AP (Triapine) improved the efficacy of TMZ therapy in patient-derived xenograft (PDX) models. [Read the Full Post]

Tryptophan metabolism induced by TDO2 promotes prostatic cancer chemotherapy resistance in a AhR/c-Myc dependent manner

198 | Oct 25 2023

Elevated expression of tryptophan 2,3-dioxygenase 2 (TDO2) promotes tryptophan metabolism and kynurenine production, activating the AhR/c-Myc/ABC-SLC transporters signaling pathway and contributing to chemoresistance in prostatic cancer. [Read the Full Post]

Pak1 pathway hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer

104 | Oct 23 2023

This study demonstrates that p21-activated kinase 1 (Pak1) plays a crucial role in resistance to estrogen receptor antagonists and CDK4/6 inhibitors in estrogen receptor-positive (ER+) breast cancer, suggesting the potential for Pak1 inhibitors as a therapeutic approach for patients with ER+ breast cancer who have become resistant to current treatments. [Read the Full Post]

[p53 regulates primordial follicle activation through the mTOR signaling pathway]

179 | Oct 22 2023

This study demonstrated that p53 inhibits primordial follicle activation through the mTOR signaling pathway, thereby maintaining the reserve of primordial follicles. [Read the Full Post]

Purine Antimetabolites associated Pneumocystis Jiroveci Pneumonia

174 | Oct 20 2023

The retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database revealed a significant safety signal for pneumocystis jiroveci pneumonia (PJP) associated with purine antimetabolites, particularly fludarabine and thioguanine, among populations with autoimmune disorders and cancer. [Read the Full Post]

Targeting eIF4F translation initiation complex with SBI-756 sensitises B lymphoma cells to venetoclax

118 | Oct 20 2023

The study demonstrated that the combination of the cap-dependent mRNA translation inhibitor SBI-756 with venetoclax enhances apoptosis and efficacy in DLBCL and MCL cells, highlighting a potential novel treatment approach for aggressive lymphomas. [Read the Full Post]

Improved antitumor activity against prostate cancer via synergistic targeting of Myc and GFAT-1

115 | Oct 19 2023

Simultaneous targeting of Myc and GFAT-1 using inhibitors and a nanocarrier delivery system shows promise as a novel strategy for the treatment of prostate cancer. [Read the Full Post]

AURKB Enhances Chromosomal Remodeling of Telomeric Genes and Accelerates Tumorigenesis of Uveal Melanoma

70 | Oct 18 2023

AURKB inhibitors show promise as a therapeutic strategy for uveal melanoma by epigenetically silencing the expression of the oncogenic telomerase reverse transcriptase (TERT). [Read the Full Post]

Targeting the DNA Damage Response and DNA Repair Pathways to Enhance Radiosensitivity in Colorectal Cancer

84 | Oct 17 2023

Targeting DNA damage response and repair pathways with inhibitors of cell-cycle checkpoint proteins represents a promising strategy to overcome radioresistance and improve the sensitivity of colorectal cancer cells to radiotherapy, with potential for combination therapies involving immunotherapy. [Read the Full Post]

VPS34-IN1 induces apoptosis of ER+ breast cancer cells via activating PERK/ATF4/CHOP pathway

151 | Oct 14 2023

VPS34-IN1, a selective inhibitor of Class III Phosphatidylinositol 3-kinase (PI3K), exhibits an antitumor effect in estrogen receptor positive (ER+) breast cancer by activating the PERK/ATF4/CHOP pathway of endoplasmic reticulum (ER) stress to induce apoptosis in breast cancer cells. [Read the Full Post]

Potential New Therapeutic Approaches for Cisplatin-Resistant Testicular Germ Cell Tumors

98 | Oct 14 2023

The proteasome inhibitor MG-132 shows promise as a potential new drug for treating cisplatin-resistant testicular germ cell tumors (TGCTs), enhancing sensitivity to cisplatin and inducing apoptosis in both parental and resistant cell lines. [Read the Full Post]

Atypical Anti-Glomerular Basement Membrane Nephritis After the First Dose of the Severe Acute Respiratory Syndrome Coronavirus 2 mRNA Vaccine

100 | Oct 13 2023

Atypical anti-GBM nephritis, which can occur after the administration of the SARS-CoV-2 mRNA vaccine, is characterized by linear IgG deposition in the glomerular basement membrane without circulating anti-GBM antibodies or lung involvement, and its response to immunosuppressive therapy is uncertain. [Read the Full Post]

Pharmacological Inhibition of p-21 Activated Kinase (PAK) Restores Impaired Neurite Outgrowth and Remodeling in a Cellular Model of Down Syndrome

129 | Oct 12 2023

In a cellular model of Down syndrome, overexpression of APP and subsequent PAK1 hyperphosphorylation impair neurite outgrowth and remodeling, suggesting PAK1 as a potential pharmacological target for intervention. [Read the Full Post]

With-No-Lysine Kinase 1 (WNK1) Augments TRPV4 Function in the Aldosterone-Sensitive Distal Nephron

97 | Oct 11 2023

WNK1 kinase plays a critical role in regulating TRPV4 activity and expression, essential for maintaining potassium homeostasis in the aldosterone-sensitive distal nephron. [Read the Full Post]

Synergistic targeting of CHK1 and mTOR in MYC-driven tumors

109 | Oct 11 2023

Simultaneous targeting of CHK1 and mTOR emerges as a novel and potent co-treatment modality for MYC-mediated tumors, impairing cell viability and inducing synergistic lethality in vitro and impeding tumor progression in vivo. [Read the Full Post]

Anti-hepatocellular carcinoma activity of the cyclin-dependent kinase inhibitor AT7519

140 | Oct 07 2023

The research findings suggest that AT7519, a CDK inhibitor, shows potential as a monotherapy or in combination with drugs like gefitinib or cabozantinib, to improve the effectiveness of treatments for hepatocellular carcinoma. [Read the Full Post]

Application of sulfoximines in medicinal chemistry from 2013 to 2020

39 | Oct 06 2023

The comprehensive review of relevant articles on sulfoximines' potency and pharmacokinetic properties from 2013 to the present aims to support the incorporation of the sulfoximine component into the toolkit of medicinal chemists by addressing the limited experience in physicochemical and in vitro parameters of sulfoximines. [Read the Full Post]

The First Case of Human Hepatic Fasciolosis Presented as Hepatic Pseudotumor Histopathologically Diagnosed in Romania-A Case Report

75 | Oct 05 2023

The case report highlights the importance of considering fasciolosis as a potential diagnosis even in areas where it is not commonly observed, emphasizing the need for careful evaluation in patients presenting with relevant symptoms. [Read the Full Post]

Nr4a1 promotes renal interstitial fibrosis by regulating the p38 MAPK phosphorylation

94 | Oct 05 2023

Nr4a1 promotes renal fibrosis by activating p38 MAPK, as evidenced by its upregulation in a mouse model of renal interstitial fibrosis, its correlation with fibrotic protein levels, and the exacerbation of fibrosis by Nr4a1 activation and its inhibition by p38 MAPK blockade. [Read the Full Post]

Translation-dependent skin hyperplasia is promoted by type 1/17 inflammation in psoriasis

153 | Oct 05 2023

This study reveals that the molecule eukaryotic initiation factor 4E (eIF4E) plays a crucial role in the abnormal differentiation of keratinocytes driven by type 1/17 inflammation in psoriasis, suggesting its potential as a therapeutic target. [Read the Full Post]

Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments

0 | Oct 04 2023

The review discusses the development of selective CDK9 inhibitors and PROTAC degraders for cancer treatment, emphasizing the need for further research to understand their mechanisms and identify suitable tumor genotypes and combination treatments. [Read the Full Post]

Discovery of a novel RIPK2 inhibitor for the treatment of inflammatory bowel disease

79 | Oct 03 2023

The novel RIPK2 inhibitor Zharp2-1 shows promising potential for the treatment of inflammatory bowel disease (IBD) based on its ability to effectively block RIPK2 kinase function, inhibit NOD-mediated signaling, and ameliorate colitis symptoms in preclinical studies. [Read the Full Post]

Effectiveness of netarsudil 0.02% in lowering intraocular pressure in patients with secondary glaucoma

133 | Oct 01 2023

Netarsudil, 0.02%, was found to be effective in lowering intraocular pressure (IOP) in patients with secondary forms of glaucoma, especially uveitic glaucoma. [Read the Full Post]

KRASG12C mutation-induced TOPK overexpression contributes to tumour progression in non-small cell lung cancer

95 | Sep 30 2023

The study reveals that the KRAS-TOPK axis contributes to the progression of non-small cell lung cancer (NSCLC) with the KRASG12C mutation, and targeting this axis could enhance the anticancer effects of existing chemotherapeutics. [Read the Full Post]

RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer

203 | Sep 27 2023

RNF112 suppresses gastric cancer progression by directly ubiquitinating FOXM1, making the RNF112/FOXM1 axis a potential prognostic biomarker and therapeutic target in gastric cancer. [Read the Full Post]

Effectiveness of netarsudil 0.02% in lowering intraocular pressure in patients with secondary glaucoma

181 | Sep 27 2023

Netarsudil, 0.02%, was found to effectively lower intraocular pressure in patients with secondary forms of glaucoma, particularly uveitic glaucoma, based on a retrospective study. [Read the Full Post]

Rapid adaptation to CDK2 inhibition exposes intrinsic cell-cycle plasticity

0 | Sep 26 2023

CDK2 inhibitors in preclinical models reveal that acute inhibition of CDK2 leads to rapid loss of substrate phosphorylation, which is compensated by CDK4/6 activity to sustain cell cycle progression, suggesting that co-inhibition of CDK2 and CDK4/6 may be necessary for effective suppression of CDK2-driven cancers. [Read the Full Post]

Discovery and resistance mechanism of a selective CDK12 degrader

66 | Sep 24 2023

The study presents the development of a CDK12-specific degrader, BSJ-4-116, which selectively degrades CDK12, resulting in premature cleavage and poly(adenylation) of DNA-damage response genes, and exhibits potent antiproliferative effects alone and in combination with olaparib, but resistance mutations in CDK12 were identified as potential mechanisms for tumor cells to evade the degrader. [Read the Full Post]

FOXM1 augments sorafenib resistance and promotes progression of hepatocellular carcinoma by epigenetically activating KIF23 expression

53 | Sep 19 2023

The study revealed that upregulation of FOXM1 in hepatocellular carcinoma (HCC) cells contributes to sorafenib resistance and HCC progression by increasing the expression of KIF23, and targeting FOXM1 could be an effective treatment strategy for HCC. [Read the Full Post]

Acetylation regulates the nucleocytoplasmic distribution and oncogenic function of karyopherin alpha 2 in lung adenocarcinoma

173 | Sep 18 2023

The acetylation of KPNA2 by CBP/p300 promotes cytosolic localization and suppresses its oncogenic activity in lung cancer cells. [Read the Full Post]

Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy

159 | Sep 17 2023

VX-970 (berzosertib or M6620) is a promising small-molecule ATR inhibitor that shows potential as an effective anticancer drug, both as monotherapy and in combination with chemotherapy or radiotherapy strategies, based on preclinical data and ongoing phase I/II clinical trials. [Read the Full Post]

Selective inhibition of ATM-dependent double-strand break repair and checkpoint control synergistically enhances the efficacy of ATR inhibitors

168 | Sep 17 2023

Inhibition of ATR kinase and simultaneous suppression of ATM kinase synergistically enhance cancer cell death and show promise as a novel combination approach for cancer therapy. [Read the Full Post]

Indirect treatment comparison of lurbinectedin versus other second-line treatments for small-cell lung cancer

62 | Sep 15 2023

Lurbinectedin showed superior survival benefit and a favorable safety profile compared to other second-line treatments for platinum-sensitive small-cell lung cancer (SCLC). [Read the Full Post]

Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments

75 | Sep 14 2023

This review discusses the development of selective CDK9 inhibitors and PROTAC degraders for the treatment of cancer, highlighting their structures, inhibitory effects, and the need for further research to explore their efficacy in specific tumor genotypes and combination regimens. [Read the Full Post]

Unique osteogenic profile of bone marrow stem cells stimulated in perfusion bioreactor is Rho-ROCK-mediated contractility dependent

61 | Sep 14 2023

This study demonstrates that fluid shear stress in a 3D dynamic culture system induces increased actomyosin contractility, upregulation of mechanoreceptors and focal adhesions, and promotes a unique osteogenic profile in bone marrow mesenchymal stem/stromal cells (BMSC), highlighting the importance of mechanical cues in regulating BMSC behavior for potential clinical applications in bone regeneration. [Read the Full Post]

Anti-Klebsiella pneumoniae activity of secondary metabolism of Achromobacter from the intestine of Periplaneta americana

121 | Sep 13 2023

This study identifies a strain of Achromobacter from the intestinal tract of Periplaneta americana that exhibits strong antibacterial activity against Klebsiella pneumoniae, highlighting the potential for the development of novel antimicrobial compounds from insect intestinal microorganisms. [Read the Full Post]

Detection of Ras nanoclustering-dependent homo-FRET using fluorescence anisotropy measurements

142 | Sep 12 2023

Fluorescence anisotropy-based homo-FRET measurements using Ras-derived constructs labeled with a single fluorescent protein provide a sensitive and advantageous approach to investigate Ras nanoclustering and assess modulators of functional Ras membrane organization. [Read the Full Post]

Ursolic acid-downregulated long noncoding RNA ASMTL-AS1 inhibits renal cell carcinoma growth via binding to HuR and reducing vascular endothelial growth factor expression

102 | Sep 12 2023

The study found that ursolic acid (UA) inhibits renal cell carcinoma (RCC) growth and tumorigenesis by downregulating ASMTL-AS1, which destabilizes VEGF mRNA and suppresses RCC cell migration, invasion, and angiogenesis. [Read the Full Post]

Norepinephrine as the Intrinsic Contributor to Contact Lens-Induced Pseudomonas aeruginosa Keratitis

166 | Sep 11 2023

This study reveals that norepinephrine, acting through the β2-adrenergic receptor, promotes Pseudomonas aeruginosa keratitis during contact lens wear, suggesting potential therapeutic targets for treating the condition. [Read the Full Post]

Inhibition-of-BUB1-Kinase-by-BAY-1816032-Sensitizes-Tumor-Cells-toward-Taxanes-ATR-and-PARP-Inhibitors-In-Vitro-and-In-Vivo

97 | Sep 11 2023

The study revealed that overexpression of BUB1 in osteosarcoma is associated with poor clinical outcomes and that inhibiting BUB1 significantly suppresses tumor growth and metastasis while inducing apoptosis, highlighting its potential as a therapeutic target. [Read the Full Post]

Activation of the integrated stress response (ISR) pathways in response to Ref-1 inhibition in human pancreatic cancer and its tumor microenvironment

80 | Sep 09 2023

Inhibition of Ref-1 redox signaling and activation of the integrated stress response (ISR) pathway through eIF2 phosphorylation could represent a promising therapeutic approach for treating pancreatic ductal adenocarcinoma (PDAC). [Read the Full Post]

Degradation of MYC by the mutant p53 reactivator drug, COTI-2 in breast cancer cells

95 | Sep 08 2023

The study demonstrated that the mutant p53 reactivating drug COTI-2 effectively degraded MYC protein and showed synergistic growth inhibition when combined with an MYC inhibitor, suggesting its potential as a broad-spectrum anticancer therapy. [Read the Full Post]

A randomized trial of eribulin monotherapy versus eribulin plus anlotinib in patients with locally recurrent or metastatic breast cancer

146 | Sep 08 2023

The combination of eribulin and anlotinib demonstrated improved progression-free survival and disease control rates compared to eribulin monotherapy in patients with HER2-negative locally recurrent or metastatic breast cancer, suggesting it as a potential alternative treatment option. [Read the Full Post]

Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras

0 | Sep 08 2023

Research has led to the development of targeted therapies, including KRAS G12C-directed drugs and SOS1 inhibitors, with potential for treating specific mutations in lung, pancreatic, and colon cancers. [Read the Full Post]

Structural Mass Spectrometry Probes the Inhibitor-Induced Allosteric Activation of CDK12/CDK13-Cyclin K Dissociation

83 | Sep 07 2023

The integration of lysine reactivity profiling (LRP) and native MS (nMS) enables the systematic investigation of dynamic molecular interactions and overall protein assembly in CDK12/CDK13-CycK complexes, providing valuable insights for the rational design of effective kinase inhibitors. [Read the Full Post]

Treg-targeted efficient-inducible platform for collagen-induced arthritis treatment

114 | Sep 07 2023

The study successfully developed a chitosan-stabilized nanoparticle drug delivery system (NDDS) capable of efficiently inducing regulatory T cells (Tregs), which showed promising results in alleviating the severity and progression of rheumatoid arthritis (RA) by restoring the equilibrium of Treg/Th17 cells. [Read the Full Post]

RUNX1 isoform disequilibrium promotes the development of trisomy 21-associated myeloid leukemia

77 | Sep 07 2023

The study proposes that an imbalance of RUNX1 isoforms, particularly elevated expression of RUNX1A, in combination with the Gata1s mutation, contributes to the development of myeloid leukemia associated with Down syndrome (ML-DS), and restoring the equilibrium between RUNX1A and RUNX1C holds potential for targeted therapies. [Read the Full Post]

Early changes in circulating cell free KRAS G12C predicts response to adagrasib in KRAS mutant non-small cell lung cancer patients

165 | Sep 06 2023

Early changes in circulating tumor DNA (ctDNA) levels of KRAS G12C, assessed approximately three weeks into treatment, can predict the likelihood of a favorable objective clinical response in patients with advanced, KRAS G12C mutant lung cancer. [Read the Full Post]

The Therapeutic Landscape for KRAS-Mutated Colorectal Cancers

125 | Sep 06 2023

The development of selective inhibitors targeting KRAS mutations, such as the FDA-approved Sotorasib and Adagrasib, has shown promise in treating colorectal cancer, but further research is needed to optimize their efficacy and overcome treatment resistance. [Read the Full Post]

CDK7 controls E2F- and MYC-driven proliferative and metabolic vulnerabilities in multiple myeloma

67 | Sep 04 2023

In pre-clinical studies, therapeutic targeting of CDK7 using the covalent small molecule inhibitor YKL-5-124 has shown promising results by inhibiting E2F and MYC transcriptional programs, impairing glycolysis, and inducing tumor regression in multiple myeloma mouse models. [Read the Full Post]

Targeting cryptic-orthosteric site of PD-L1 for inhibitor identification using structure-guided approach

135 | Sep 03 2023

This study utilized structure-assisted virtual screening and molecular dynamics simulations to identify two novel small molecule compounds as potential therapeutic candidates for inhibiting the PD-L1 protein-protein interaction in cancer treatment. [Read the Full Post]

REV1 promotes lung tumorigenesis by activating the Rad18/SERTAD2 axis

101 | Sep 02 2023

The study suggests that REV1 is a potential diagnostic marker and therapeutic target for lung cancer, and the novel REV1 inhibitor, JH-RE-06, shows promise as a safe and efficient therapeutic agent for NSCLC. [Read the Full Post]

Development of Highly Potent and Selective Pyrazolopyridine Inhibitor of CDK8/19

0 | Aug 31 2023

JH-XVI-178 (compound 15) is a highly potent and selective inhibitor of CDK8/19, overcoming metabolic challenges and displaying favorable pharmacokinetic properties. [Read the Full Post]

SEL120-34A is a novel CDK8 inhibitor active in AML cells with high levels of serine phosphorylation of STAT1 and STAT5 transactivation domains

58 | Aug 31 2023

SEL120-34A, a substituted tricyclic benzimidazole and inhibitor of Cyclin-dependent kinase 8 (CDK8), shows promise as a personalized therapeutic approach in acute myeloid leukemia (AML) by targeting oncogenic transcriptional programs through inhibition of STAT5 phosphorylation. [Read the Full Post]

Targeting KRAS in pancreatic cancer: Emerging therapeutic strategies

132 | Aug 30 2023

This chapter provides an overview of KRAS biochemistry, signaling pathways, different mutations, emerging KRAS-targeted therapies, combination strategies, challenges in KRAS targeting, and future directions with a specific emphasis on pancreatic cancer. [Read the Full Post]

Clinical Characterization of Targetable Mutations (BRAF V600E and KRAS G12C) in Advanced Colorectal Cancer-A Nation-Wide Study

179 | Aug 30 2023

The retrospective analysis revealed that BRAF V600E mutation in metastatic colorectal cancer is associated with factors such as female sex, right colon primary location, and specific histological features, while KRAS G12C mutation is linked to left colon primary tumors and brain metastases, suggesting potential therapeutic targets and the need for further investigation. [Read the Full Post]

Evaluation of KRASG12C inhibitor responses in novel murine KRASG12C lung cancer cell line models

172 | Aug 30 2023

The generation of three novel murine KRASG12C-driven lung cancer cell lines provides valuable models for studying and improving therapeutic combination strategies with KRASG12C inhibitors. [Read the Full Post]

Therapeutic inhibition of Bmi-1 ablates chemoresistant cancer stem cells in adenoid cystic carcinoma

125 | Aug 29 2023

Targeting Adenoid Cystic Carcinoma (ACC) Cancer Stem Cells (CSCs) with Bmi-1 inhibitors, such as PTC596, demonstrates the potential to overcome chemoresistance and prevent tumor relapse in ACC. [Read the Full Post]

Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras

157 | Aug 29 2023

The development of KRAS G12C-directed drugs and SOS1 inhibitors represents promising approaches for targeting mutated oncogenes in lung, pancreatic, and colon cancers. [Read the Full Post]

PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis

118 | Aug 26 2023

The study identified multidrug-resistant CLL cells in patients and demonstrated that a small molecule activator of PP2A called DT-061 induced apoptosis in these cells independently of Bax/Bak, providing a potential strategy to overcome treatment resistance. [Read the Full Post]

Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis

90 | Aug 26 2023

AK-01, a highly selective AURKA inhibitor, demonstrates potent tumor suppression through apoptosis and cell cycle arrest in MCPyV-negative Merkel cell carcinoma cells without RB expression, highlighting its potential as a promising therapeutic option for MCC management. [Read the Full Post]

The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage

127 | Aug 25 2023

The study demonstrates that targeted degradation of BET proteins using dBET6 effectively inhibits the cGAS-STING pathway in reactive retinal macrophages/microglia, providing neuroprotective effects and suggesting a potential therapeutic approach for retinal degenerative diseases. [Read the Full Post]

CDK9 inhibition induces epigenetic reprogramming revealing strategies to circumvent resistance in lymphoma

85 | Aug 22 2023

AZD4573, a selective inhibitor of CDK9, demonstrates effectiveness in restricting DLBCL cell growth by inducing transcriptional and epigenetic changes, and its combination with PIM kinase or PI3K inhibitors shows promise in overcoming resistance and reducing tumor progression in DLBCL. [Read the Full Post]

The CDK7 inhibitor CT7001 (Samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer

94 | Aug 22 2023

The study demonstrates that the CDK7 inhibitor CT7001 shows promising antitumor efficacy in castration-resistant prostate cancer (CRPC), inhibiting cell proliferation, inducing apoptosis, and suppressing androgen receptor (AR) signaling, both as a monotherapy and in combination with the antiandrogen enzalutamide. [Read the Full Post]

CSF-1R inhibitor, pexidartinib, sensitizes esophageal adenocarcinoma to PD-1 immune checkpoint blockade in a rat model

0 | Aug 11 2023

This study demonstrates that pexidartinib, a CSF-1R inhibitor, alone or in combination with a PD-1 inhibitor, shows significant tumor shrinkage and enhanced antitumor immune responses in a rat model of esophageal adenocarcinoma, providing a promising combinatorial strategy for future clinical approaches. [Read the Full Post]

A PDX model combined with CD-DST assay to evaluate the antitumor properties of KRpep-2d and oxaliplatin in KRAS (G12D) mutant colorectal cancer

103 | Aug 06 2023

The combination of patient-derived xenograft (PDX) models and the collagen gel droplet embedded culture drug sensitivity test (CD-DST) offers a comprehensive and feasible approach for evaluating the antitumor properties of compounds, as demonstrated by the significant inhibitory effects of oxaliplatin but lack of effectiveness of KRpep-2d in both tests. [Read the Full Post]

Interplay of the transcription factor MRTF-A and matrix stiffness controls mammary acinar structure and protrusion formation

63 | Aug 05 2023

The study found that matrix stiffness influences the formation of invasive protrusions in mammary acini, with increased MRTF-A activity observed on stiff matrices, highlighting the intricate interplay between matrix properties and transcription factors in mammary gland development. [Read the Full Post]

NAD + Metabolism Generates a Metabolic Vulnerability in Endocrine-Resistant Metastatic Breast Tumors in Females

177 | Aug 03 2023

The study revealed that combining a NAMPT inhibitor with fulvestrant showed a synergistic effect in reducing metastatic tumor burden and reversing gene expression associated with aggressive tumor phenotypes in ER+ metastatic breast cancer, offering a promising strategy for treatment. [Read the Full Post]

KIF11 is a potential prognostic biomarker and therapeutic target for adrenocortical carcinoma

112 | Aug 02 2023

The study demonstrated that the overexpression of KIF11 in adrenocortical carcinoma (ACC) is associated with poor prognosis and suggests that KIF11 may serve as a potential therapeutic target for ACC. [Read the Full Post]

Increased CMV disease and "severe" BK viremia with belatacept vs. sirolimus three-drug maintenance immunosuppression

64 | Aug 02 2023

The study found that belatacept therapy in kidney transplant recipients was associated with a higher risk of CMV disease and "severe" CMV and BK viremia, but did not significantly increase overall infection incidence and showed comparable rates of acute rejection and graft loss at 12 months compared to sirolimus therapy. [Read the Full Post]

Development of Highly Potent and Selective Pyrazolopyridine Inhibitor of CDK8/19

48 | Jul 31 2023

JH-XVI-178 (compound 15) is a highly potent and selective inhibitor of CDK8/19 with low clearance and moderate oral pharmacokinetic properties, developed through a hybridization approach starting from CCT251921 and MSC2530818. [Read the Full Post]

Sevoflurane induces neurotoxic effects on developing neurons through the WNK1/NKCC1/Ca2+ /Drp-1 signalling pathway

67 | Jul 30 2023

The study found that sevoflurane-induced neurotoxicity in hippocampal neuronal cells is mediated through the WNK1/NKCC1/Ca2+/Drp-1 signaling pathway, and inhibiting this pathway can alleviate cell viability reduction and apoptosis caused by sevoflurane exposure. [Read the Full Post]

MAPK-interacting kinases inhibition by eFT508 overcomes chemoresistance in preclinical model of osteosarcoma

274 | Jul 26 2023

The study highlights the therapeutic potential of eFT508, a selective inhibitor of MNK1/2, alone and in combination with paclitaxel, as a promising treatment for osteosarcoma by inhibiting tumor growth and demonstrating selectivity and synergistic effects. [Read the Full Post]

Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment

212 | Jul 26 2023

Tomivosertib (eFT-508) demonstrates promising efficacy both in vitro and in vivo, including synergistic effects with adriamycin, suggesting its potential as a more efficacious therapeutic option for patients with triple-negative breast cancer (TNBC). [Read the Full Post]

The mRNA-binding protein DDX3 mediates TGF-β1 upregulation of translation and promotes pulmonary fibrosis

85 | Jul 25 2023

Inhibiting the mRNA-binding protein DDX3, which mediates TGF-β1 upregulation of translation, shows promise in reducing pulmonary fibrosis and associated inflammation in experimental models. [Read the Full Post]

Checkpoint kinase‑1 inhibition and etoposide exhibit a strong synergistic anticancer effect on chronic myeloid leukemia cell line K562 by impairing homologous recombination DNA damage repair

95 | Jul 25 2023

In summary, the study demonstrates that silencing CHK1 or inhibiting its activity, in combination with chemotherapy, shows promise as an effective strategy for enhancing the cytotoxic effects and overcoming chemotherapeutic resistance in chronic myeloid leukemia (CML). [Read the Full Post]

Treating colorectal peritoneal metastases with an injectable cytostatic loaded supramolecular hydrogel in a rodent animal model

123 | Jul 21 2023

The experimental study demonstrated that treatment of peritoneal metastases with a supramolecular hydrogel loaded with mitomycin C (MMC) significantly improved overall survival compared to treatment with free MMC alone, suggesting the potential of this drug delivery system for enhancing therapeutic efficacy. [Read the Full Post]

Oncogenic KRAS G12C: Kinetic and redox characterization of covalent inhibition

86 | Jul 21 2023

The recent study reveals that the C12 thiol in KRASG12C exhibits a depressed pKa and susceptibility to chemical ligation, as well as oxidation, providing insights for drug discovery and indicating the occurrence of unknown biological consequences. [Read the Full Post]

Proof of concept for poor inhibitor binding and efficient formation of covalent adducts of KRASG12C and ARS compounds

106 | Jul 21 2023

This computational study provides a comprehensive understanding of the reaction mechanism and kinetic constants involved in the covalent binding of ARS-853 to the KRASG12C·GDP complex, offering insights into the design of selective covalent inhibitors for challenging RAS-like proteins. [Read the Full Post]

The tumor stroma influences immune cell distribution and recruitment in a PDAC-on-a-chip model

199 | Jul 20 2023

This study utilized a 3D PDAC model to investigate the interaction between tumor stroma and immune cells, revealing that stromal cells create a physical and biochemical barrier that hinders immune cell infiltration, and targeting the stroma can increase immune cell infiltration, offering potential therapeutic strategies for PDAC. [Read the Full Post]

Icaritin inhibits CDK2 expression and activity to interfere with tumor progression

48 | Jul 17 2023

Icaritin directly targets CDK2 in tumor cells, leading to downregulation of CDK2 activity, inhibition of cell cycle progression, and promotion of apoptosis, suggesting its potential as a therapeutic agent for cancer treatment. [Read the Full Post]

Specific gene module pair-based target identification and drug discovery

0 | Jul 14 2023

The GMPTI method extracts target-induced gene modules to identify target signatures and predict novel compound-target interactions, leading to the discovery of novel inhibitors for three proteins in the PI3K pathway. [Read the Full Post]

Kinesin Family Member C1 Overexpression Exerts Tumor-Promoting Properties in Head and Neck Squamous Cell Carcinoma via the Rac1/Wnt/β-catenin Pathway

89 | Jul 13 2023

Abnormal upregulation of Kinesin family member C1 (KIFC1) in head and neck squamous cell carcinoma (HNSCC) is regulated by N6-methyladenosine (m6A) RNA methylation via interaction with demethylase alkB homolog 5, promoting HNSCC progression through activation of the Rac1/Wnt/β-catenin pathway. [Read the Full Post]

Topical Ripasudil for the Treatment of Segmental Corneal Edema: A Case Series

198 | Jul 10 2023

Topical ripasudil has shown promising results in improving vision and resolving corneal edema in patients with focal corneal edema following anterior segment surgeries, serving as an effective treatment option that may reduce the need for endothelial transplantation. [Read the Full Post]

Ripasudil-Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials

140 | Jul 10 2023

The results of the study demonstrated that the ripasudil-brimonidine fixed-dose combination (RBFC) had a greater ability to lower intraocular pressure (IOP) compared to ripasudil or brimonidine alone. [Read the Full Post]

Efficacy of favipiravir against influenza virus resistant to both baloxavir and neuraminidase inhibitors

117 | Jul 09 2023

The study findings suggest that favipiravir should be used as a treatment option for patients suspected of having influenza virus infections resistant to NA inhibitors and baloxavir. [Read the Full Post]

A Facile Raman Spectroscopy Method for Online Monitoring of Crystal Plane Orientation of Favipiravir

173 | Jul 09 2023

This paper describes a facile method for online monitoring of the crystal plane orientation of favipiravir using Raman spectroscopy, providing a non-contact, fast, and sample preparation-free approach with potential applications in pharmaceutical processes. [Read the Full Post]

Comparative transcriptome profile of mouse macrophages treated with the RhoA/Rock pathway inhibitors Y27632, Fingolimod (Gilenya), and Rezurock (Belumosudil, SLx-2119)

113 | Jul 07 2023

The transcriptome profiling study comparing macrophages treated with Y27632, Fingolimod, and Rezurock revealed distinct downregulation of GTPase and actin pathways in cell migration for Y27632 and Fingolimod, while Rezurock specifically downregulated fibrosis-related genes, providing insights into the differences in their anti-chronic rejection properties and aiding in the development of targeted therapies. [Read the Full Post]

Discovery of indoline-based derivatives as effective ROCK2 inhibitors for the potential new treatment of idiopathic pulmonary fibrosis

163 | Jul 07 2023

A new series of selective ROCK2 inhibitors based on indoline, particularly compound 9b, showed promising results in inhibiting collagen gel contraction, suppressing fibrotic markers, and exhibiting anti-pulmonary fibrosis effects in a bleomycin-induced IPF rat model, suggesting its potential as a lead compound for IPF treatment. [Read the Full Post]

A retrospective cohort study on the efficacy and safety for combination therapy of immunotherapy, targeted agent, and chemotherapy versus immunochemotherapy or chemotherapy alone in the first-line treatment of advanced biliary tract carcinoma

79 | Jul 05 2023

This retrospective study suggests that combining anti-PD-1/PD-L1 immunotherapy with anlotinib and gemcitabine shows promising efficacy and an acceptable safety profile in patients with advanced biliary tract carcinoma. [Read the Full Post]

On-chip real-time impedance monitoring of hiPSC-derived and artificial basement membrane-supported endothelium

157 | Jul 05 2023

Electrochemical impedance spectroscopy was successfully applied to monitor the stability and integrity of a human induced pluripotent stem cell-derived endothelial barrier supported by an artificial basement membrane, revealing enhanced stability in a serum-free and bromodeoxyuridine-containing culture medium and sensitivity to stimuli such as thrombin. [Read the Full Post]

Targeting glutamine metabolism with photodynamic immunotherapy for metastatic tumor eradication

100 | Jul 04 2023

The study presents a novel photodynamic immunostimulant, BVC, that reprograms glutamine metabolism and combines immune checkpoint blockade therapy with photodynamic therapy to enhance immune recognition and prevent immune escape for the eradication of metastatic tumors. [Read the Full Post]

Design, synthesis, and evaluation of PD-1/PD-L1 small-molecule inhibitors bearing a rigid indane scaffold

131 | Jul 04 2023

Compound D3, a novel small-molecule inhibitor of the PD-1/PD-L1 interaction, demonstrates potent inhibitory activity and immune-enhancing effects, making it a promising candidate for further development in immunotherapy. [Read the Full Post]

Proof of concept nanotechnological approach to in vitro targeting of malignant melanoma for enhanced immune checkpoint inhibition

103 | Jul 04 2023

The study demonstrates that the delivery of a small molecule inhibitor of the PD-1/PD-L1 pathway using nanodiamond-based nanoparticles enhances immune cell stimulation and promotes stronger interactions between immune cells and melanoma cells, suggesting potential for improved melanoma therapy. [Read the Full Post]

Rapid adaptation to CDK2 inhibition exposes intrinsic cell-cycle plasticity

61 | Jun 29 2023

Co-inhibition of CDK2 and CDK4/6 may be required to suppress adaptation to CDK2 inhibitors and effectively target the proliferative program in cancer cells. [Read the Full Post]

Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts

57 | Jun 26 2023

Targeting telomeres through TERT inhibition shows promise as a potential therapeutic strategy for reducing tumor growth and improving outcomes in non-small cell lung cancer (NSCLC). [Read the Full Post]

Bridging Gaps in HDR Improvement: The Role of MAD2L2, SCAI, and SCR7

127 | Jun 25 2023

This study demonstrated that MAD2L2 knockdown and SCR7 treatment significantly improved homology-directed repair (HDR) efficiency during CRISPR/Cas-mediated genome editing, offering valuable insights for enhancing precise correction in gene editing. [Read the Full Post]

Modulation of blood-brain tumor barrier for delivery of magnetic hyperthermia to brain cancer

163 | Jun 25 2023

This proposed approach utilizes a polymeric nanocarrier to deliver fingolimod and modulate the blood-brain tumor barrier, allowing for targeted accumulation of magnetic nanoclusters and synergistic magnetic hyperthermia therapy for the treatment of glioblastoma [Read the Full Post]

Expression of RNA polymerase I catalytic core is influenced by RPA12

76 | Jun 24 2023

The study demonstrates that while RPA12 influences the basal expression and localization of the Pol I subunits RPA194 and RPA135, it does not affect their interaction or the transcriptional activity of Pol I, and the degradation of RPA194 induced by the small-molecule inhibitor BMH-21 is independent of RPA12. [Read the Full Post]

Short-term follow-up pilot study of sole middle meningeal artery embolization for chronic subdural hematoma: influence of internal architecture on the radiological outcomes

124 | Jun 24 2023

The study found that patients with separated chronic subdural hematoma (CSDH) architecture had a lower rate of achieving the radiological endpoint and a slower rate of volume reduction compared to other CSDH types when treated with middle meningeal artery embolization (MMAE). [Read the Full Post]

Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer

94 | Jun 23 2023

[Read the Full Post]

TK216 targets microtubules in Ewing sarcoma cells

103 | Jun 22 2023

The study reveals that TK216, initially developed as an EWSR1-FLI1 inhibitor, acts as a microtubule destabilizing agent, explaining its cytotoxicity and supporting a reevaluation of its clinical trials in combination with vincristine. [Read the Full Post]

The role of small GTPases in bisphenol AF-induced multinucleation in comparison with dibutyl phthalate in the male germ cells

178 | Jun 22 2023

This study demonstrates that BPAF exposure leads to cytotoxicity, increased multinucleation in mouse spermatogonia cells, and highlights the involvement of small GTPase-signaling pathways in mediating these effects, providing insights into the genotoxic mechanisms of BPA analogs on male germ cells. [Read the Full Post]

Therapeutic potential of CDK11 in cancer

187 | Jun 19 2023

The discovery that CDK11 regulates pre-mRNA splicing and the identification of OTS964 as a CDK11 inhibitor with antiproliferative properties highlight the therapeutic potential of targeting CDK11 in cancer treatment. [Read the Full Post]

Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening

0 | Jun 14 2023

Silencing CDC7 and combining the CDC7 inhibitor XL413 with chemotherapy demonstrated synergistic effects, increasing apoptosis, inducing cell cycle arrest, and improving the efficacy of chemotherapy in chemo-resistant small-cell lung cancer (SCLC) cells both in vitro and in vivo. [Read the Full Post]

Identifying the molecular mechanisms of sepsis-associated acute kidney injury and predicting potential drugs

99 | Jun 11 2023

This study utilized weighted co-expression network analysis, machine learning, immune cell correlation, and drug prediction to identify key ferroptosis genes, potential diagnostic markers, and therapeutic targets, such as miR-650 and miR-296-3p genes, OLFM4, CLU, RRM2, SLC2A3, CCL5, ADAMTS1, and EPHX2, and suggested EHT1864 and salubrinal as potential therapeutic agents for septic acute kidney injury (SA-AKI). [Read the Full Post]

Toxic hepatitis in metastatic breast cancer patient using ribociclib and denosumab

47 | Jun 09 2023

Denosumab-induced hepatotoxicity is a rare occurrence, as reported in a limited number of cases, and in the case described, liver values improved after discontinuation of denosumab. [Read the Full Post]

Characterization of Plasmodium falciparum prohibitins as novel targets to block infection in humans by impairing the growth and transmission of the parasite

217 | Jun 08 2023

The study characterizes Plasmodium falciparum prohibitins (PHBs), showing their expression in both asexual and sexual blood stages and localization in mitochondria, and demonstrating their involvement in stabilizing mitochondrial DNA and maintaining integrity, with potential druggability for blocking parasite growth using Rocaglamide (Roc-A). [Read the Full Post]

Alpha-tocopherol enhances spermatogonial stem cell proliferation and restores mouse spermatogenesis by up-regulating BMI1

100 | Jun 05 2023

This study investigates the role of BMI1 in spermatogonial stem cell proliferation and male reproduction, and demonstrates the potential modulatory effect of alpha-tocopherol on BMI1 both in vitro and in vivo. [Read the Full Post]

A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy

127 | Jun 04 2023

The study demonstrates that covalent drugs that alkylate mutated residues on oncoproteins can generate unique MHC-I-restricted neoantigens, which can be targeted with a bispecific T cell engager construct to elicit a cytotoxic T cell response against cancer cells, including those resistant to direct inhibition. [Read the Full Post]

KDELC2 Upregulates Glioblastoma Angiogenesis via Reactive Oxygen Species Activation and Tumor-Associated Macrophage Proliferation

134 | Jun 03 2023

This study demonstrates that KDELC2 promotes glioblastoma angiogenesis via the activation of multiple pathways, including NLRP3 inflammasome, autophagy, ER stress, and TAM polarization. [Read the Full Post]

Vaccines prevent reinduction of rheumatoid arthritis symptoms in collagen-induced arthritis mouse model

170 | Jun 02 2023

This study suggests that immune metabolic modulators such as paKG(PFK15 + bc2) microparticles may be a promising alternative or complementary treatment option for RA and paves the way for the development of flare-up mouse models and antigen-specific drug treatments. [Read the Full Post]

Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma

93 | Jun 01 2023

The study found that copy number gains of loci containing the STAT3/5 oncogenes are present in 74% of L-CTCL cases and identified the STAT3/5 and PAK kinase interaction as a potential therapeutic target for L-CTCL. [Read the Full Post]

Synergistic apoptotic effect of miR-183-5p and Polo-Like kinase 1 inhibitor NMS-P937 in breast cancer cells

60 | May 31 2023

This research study explores the role of miRNAs in breast cancer and their impact on breast cancer cells' response to PLK1 inhibition, with miR-183-5p targeting the PLK1 gene and enhancing the effectiveness of NMS-P937 in inducing apoptosis. [Read the Full Post]

Long non-coding RNA HIF1A-As2 and MYC form a double-positive feedback loop to promote cell proliferation and metastasis in KRAS-driven non-small cell lung cancer

151 | May 25 2023

This passage describes a study on the role of lncRNA HIF1A-As2 in regulating the activation of KRAS in lung cancer and its potential as a therapeutic target. [Read the Full Post]

Functional Assessment of Kinesin-7 CENP-E in Spermatocytes using In Vivo Inhibition, Immunofluorescence and Flow Cytometry

0 | May 21 2023

The article describes a practical and efficient in vivo inhibition method for kinesin-7 CENP-E in mouse spermatocytes via testicular injection, facilitating mechanistic studies of meiosis and potential clinical applications. [Read the Full Post]

Tyrosine Kinase Inhibitors Target B Lymphocytes

243 | May 20 2023

Protein kinase inhibitors previously used to treat ALK-positive lung cancer cells have shown potential in targeting LTK-positive B cells, providing new treatment options for autoimmune disorders and blood cancers. [Read the Full Post]

Efficient production of recombinant proteins in suspension CHO cells culture using the Tol2 transposon system coupled with cycloheximide resistance selection

75 | May 16 2023

The study demonstrates an efficient method for producing therapeutic proteins using DNA recombination techniques in mammalian cells, combining the Tol2 transposon system and cell selection by cycloheximide resistance to produce stable cell lines with constant productivity and cell growth suitable for commercial production. [Read the Full Post]

An Umpolung Approach to Acyclic 1,4-Dicarbonyl Amides via Photoredox-Generated Carbamoyl Radicals

200 | May 15 2023

This passage describes a method for the generation and reaction of carbamoyl radicals from oxamate salts followed by reaction with electron-poor olefins, which enables the mild and mass-efficient formation of 1,4-dicarbonyl products, supported by ab initio calculations, and designed to be environmentally friendly. [Read the Full Post]

Allosteric inhibition of HSP70 in collaboration with STUB1 augments enzalutamide efficacy in antiandrogen resistant prostate tumor and patient-derived models

93 | May 13 2023

The study suggests that targeting HSP70 using small-molecule inhibitors, in combination with ARSI drugs, could be a promising approach to overcome resistance to ARSI in advanced prostate cancer. [Read the Full Post]

CDK12/13 promote splicing of proximal introns by enhancing the interaction between RNA polymerase II and the splicing factor SF3B1

36 | May 09 2023

The article reports that dual inhibition of CDK12 and CDK13 impairs splicing of a subset of introns characterized by weak 3' splice sites located at larger distance from the branchpoint, and targeting both CDK12/13 and the spliceosome represents an exploitable anticancer approach. [Read the Full Post]

Characterization of a Cdc42 protein inhibitor and its use as a molecular probe

41 | May 06 2023

This passage discusses the identification and characterization of a new Cdc42-selective allosteric inhibitor, which has potential therapeutic implications for diseases related to Cdc42 overactivity and could facilitate molecular pathway studies involving GTPases. [Read the Full Post]

Chemotherapy-Resistant Breast Cancer and Carcinomatous Pleuritis Successfully Treated with Abemaciclib plus Letrozole Therapy

52 | May 05 2023

This case report describes a chemotherapy-resistant case of invasive micropapillary carcinoma in an older adult patient that was effectively treated with abemaciclib plus letrozole therapy. [Read the Full Post]

A Systematic Review of Second-Line Treatments in Antiviral Resistant Strains of HSV-1, HSV-2, and VZV

68 | May 04 2023

This study conducted a systematic review of the literature on second-line treatments for drug-resistant strains of herpes simplex viruses, and found that there are potential options that could effectively manage these infections. [Read the Full Post]

Safety and immunogenicity of a TK/ gI/gE gene-deleted feline herpesvirus-1 mutant constructed via CRISPR/Cas9 in feline

68 | Apr 28 2023

The study describes the development of a novel FHV-1 vaccine using CRISPR/Cas9-mediated homologous recombination, which showed improved safety and efficacy compared to the commercial modified live vaccine. [Read the Full Post]

Phase I clinical and pharmacological study of thymidine (NSC 21548) and cis-diamminedichloroplatinum(II) in patients with advanced cancer

88 | Apr 28 2023

A Phase I trial found that the maximally tolerated dose of thymidine plus cisplatin in patients with advanced cancer was 60 g/m2/day, with hematological toxicity being the dose-limiting factor, and recommended this dose for Phase II trials. [Read the Full Post]

Immune checkpoint inhibitors modulate the cytotoxic effect of chemotherapy in lung adenocarcinoma cells

166 | Apr 24 2023

The study found that immune checkpoint inhibitors can either potentiate or depotentiate the cytotoxic effects of chemotherapy in lung adenocarcinoma cell lines with different PD-L1 expression levels, and the specific effects vary depending on the ICIs and chemotherapy agents used. [Read the Full Post]

Insights into the mechanisms of triptolide nephrotoxicity through network pharmacology-based analysis and RNA-seq

212 | Apr 19 2023

The combination of network pharmacology and deep RNA-seq analysis provides valuable insights into the molecular mechanisms of TPL nephrotoxicity, identifying potential targets and signaling pathways for further investigation. [Read the Full Post]

Chlorogenic acid, rutin, and quercetin from Lysimachia christinae alleviate triptolide-induced multi-organ injury in vivo by modulating immunity and AKT/mTOR signal pathway to inhibit ferroptosis and apoptosis

275 | Apr 18 2023

The study showed that a combination of organ-protective ingredients from Lysimachia christinae could protect against triptolide-induced multi-organ injury in vivo by activating the AKT/mTOR pathway and reducing cell death including ferroptosis and apoptosis inhibition. [Read the Full Post]

Investigation of the impact of rosuvastatin and telmisartan in doxorubicin-induced acute cardiotoxicity

157 | Apr 15 2023

The study found that pre-treatment with rosuvastatin and telmisartan, alone or in combination, showed significant cardio-protective effects against the acute cardiotoxicity induced by doxorubicin. [Read the Full Post]

Modulation of the endoplasmic reticulum stress and unfolded protein response mitigates the behavioral effects of early-life stress

193 | Apr 13 2023

The study suggests that modulation of ER stress and UPR processes may underlie susceptibility or resilience to early-life stress (ELS) in rats. [Read the Full Post]

Lonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome

113 | Apr 06 2023

This study reports the positive effects of lonafarnib on cardiovascular structure, properties, and function in a mouse model of progeria, leading to 100% survival of treated mice and improved arterial structure and function, while rapamycin did not improve outcomes. [Read the Full Post]

The role of transforming growth factor-β2 in cigarette smoke-induced lung inflammation and injury

250 | Apr 06 2023

The study found that TGF-β2 attenuated CSE-induced IL-8 production in PBECs and alleviated lung inflammation/injury in CS-exposed mice through the Smad3 signaling pathway. [Read the Full Post]

Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus

297 | Apr 05 2023

This research demonstrates that mutations in the K-D-K-E methyltransferase motif restrict the cell-to-cell spread of Newcastle disease virus via tunnelling nanotubes. [Read the Full Post]

Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy

104 | Apr 04 2023

This study demonstrates the pathological role of non-canonical NLRC4 inflammasomes in glioma and proposes therapeutic strategies based on modulating the inflammatory tumor microenvironment. [Read the Full Post]

Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors

0 | Apr 04 2023

Sub-type selective Aurora kinase inhibitors targeting specific residues unique to either Aurora A or B may have advantages over pan-selective inhibitors and could be useful in the treatment of cancer. [Read the Full Post]

Monitoring paxillin in astrocytes reveals the significance of the adhesion GPCR VLGR1/ADGRV1 for focal adhesion assembly

192 | Apr 04 2023

VLGR1 is a vital component of focal adhesions and regulates cell migration by controlling focal adhesion turnover during their assembly, and its dysfunctions may contribute to the pathogenesis of Usher syndrome, epilepsy, and other related diseases. [Read the Full Post]

A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells

0 | Apr 03 2023

The study identifies Milciclib as a CDK7 inhibitor that blocks glucose consumption in non-small-cell lung cancer cells with an activated PI3K pathway by decreasing SLC2A1 mRNA and protein levels and inhibiting glucose transport, suggesting that targeting CDK7 may be a promising strategy for developing anti-cancer therapies. [Read the Full Post]

Differential roles of phosphatidylinositol 3-kinase/akt pathway in retinal ganglion cell survival in rats with or without acute ocular hypertension

117 | Apr 03 2023

The study demonstrated that the PI3K/akt pathway is involved in mediating RGC survival following IOP elevation but not under normal conditions, suggesting its potential as a therapeutic target for ocular ischemic injuries and glaucoma. [Read the Full Post]

The role of drug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP) and OATP1A/1B and of CYP3A4 in the pharmacokinetics of the CDK inhibitor milciclib

0 | Apr 02 2023

The study investigated the impact of transporters and enzymes on the pharmacokinetics of the anticancer drug milciclib, and found that ABCB1 and ABCG2 transporters cooperatively limit milciclib brain penetration, while OATP1 and CYP3A have only a minor impact. [Read the Full Post]

Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent

134 | Mar 31 2023

The passage describes the pharmacokinetics of geldanamycin in mice and a dog and highlights the potential for acute hepatotoxic reactions, indicating a need for further pharmacological and therapeutic information before considering the drug for clinical development. [Read the Full Post]

Inhibition of Aurora kinase A activity enhances the antitumor response of beta-catenin blockade in human adrenocortical cancer cells

46 | Mar 31 2023

Inhibition of Aurora kinases combined with blockade of the Wnt/beta-catenin pathway may provide a promising combinatorial approach for targeting ACC tumors. [Read the Full Post]

Identification of significant gene expression changes in multiple perturbation experiments using knockoffs

193 | Mar 30 2023

The approach described uses the model-X knockoffs framework and Deep Neural Networks to identify significant gene expression changes in multiple perturbation experiments, allowing for better understanding of underlying mechanisms of disease and identification of new drug targets. [Read the Full Post]

A first-in-class clinical G-quadruplex-targeting drug. The bench-to-bedside translation of the fluoroquinolone QQ58 to CX-5461 (Pidnarulex)

44 | Mar 28 2023

The development and mechanism of action of CX-3543 and CX-5461, as well as their potential clinical application in cancer therapy, highlight the promising approach of synthetic lethality for identifying cancer patients who may benefit from G-quadruplex-targeting compounds. [Read the Full Post]

Selective inhibition of HDAC6 promotes bladder cancer radiosensitization and mitigates the radiation-induced CXCL1 signalling

134 | Mar 20 2023

This study found that selective inhibition of histone deacetylase 6 (HDAC6) can enhance the radiosensitivity of bladder cancer cells and suppress radiation-induced oncogenic signaling, suggesting its potential as a therapeutic strategy in combination with radiation therapy. [Read the Full Post]

Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy

225 | Mar 18 2023

The study identified PIM kinase as a potential target for the development of novel treatments for alveolar echinococcosis, and demonstrated the utility of high-throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. [Read the Full Post]

Unusually High Affinity of the PLK Inhibitors RO3280 and GSK461364 to HSA and Its Possible Pharmacokinetic Implications

99 | Mar 17 2023

The study investigated the binding processes of two Polo-like kinase inhibitors, RO3280 and GSK461364, to the human serum albumin (HSA) protein, finding that RO3280 binds to HSA in the charge state +1 prior to a deprotonation pre-equilibrium and has a higher binding affinity for HSA than GSK461364. [Read the Full Post]

Chitosan-Enclosed Menadione Sodium Bisulfite as an Environmentally Friendly Alternative to Enhance Biostimulant Properties against Drought

107 | Mar 11 2023

The use of nanoencapsulation to deliver menadione sodium bisulfite has been shown to improve its protective properties against water deficit stress and reduce the need for continuous retreatment, highlighting the potential of nanotechnology to enhance the performance of biostimulants in agriculture. [Read the Full Post]

Emerging drug targets for sickle cell disease: shedding light on new knowledge and advances at the molecular level

138 | Mar 10 2023

Understanding early events in sickle cell disease pathogenesis associated with the presence of hemoglobin S is crucial for identifying new targets for treatment, including reducing HbS levels, reducing the impact of HbS polymers, and targeting membrane events, and exploiting the unique permeability of sickle cells for developing targeted therapies. [Read the Full Post]

DTIC (nsc-45388) and combination therapy for melanoma. I. Studies with DTIC, BCNU (NSC-409962), CCNU (NSC-79037), vincristine (NSC-67574), and hydroxyurea (NSC-32065)

112 | Mar 10 2023

The study found that combination chemotherapy regimens can improve response rates and survival times in patients with metastatic malignant melanoma, but careful monitoring of toxicity is necessary and treatment decisions should be individualized based on the patient's clinical profile. [Read the Full Post]

Evaluation of the knowledge of hematologists about the management of infectious complications in hematologic patients

108 | Mar 02 2023

The study results highlight the need for continuous education for hematologists in Brazil to improve their knowledge and understanding of infectious complications in patients with hematologic malignancies and hematopoietic cell transplant recipients. [Read the Full Post]

Effect of MXRA7 on the Biological Functions of Acute B Lymphoblastic Leukemia Cell Line REH

133 | Mar 02 2023

The study found a positive correlation between the expression of MXRA7 and acute B-ALL and suggests that knockdown of MXRA7 may be a potential target for the treatment of B-ALL by reducing cell proliferation and increasing sensitivity to cytarabine, but further research is needed to confirm its usefulness. [Read the Full Post]

Endothelial-specific targeting of RhoA signaling via CD31 antibody-conjugated nanoparticles

314 | Feb 26 2023

The study aimed to develop a CD31-targeting liposome with Fasudil, a clinically-relevant Rho kinase inhibitor, to target the RhoA signaling in endothelial cells for potential anti-angiogenic therapy by minimizing toxicity. [Read the Full Post]

Predictive factors for improvement of symptomatic cerebral vasospasm following subarachnoid hemorrhage by selective intra-arterial administration of fasudil hydrochloride

336 | Feb 26 2023

Selective intra-arterial administration of fasudil improves neurological findings in 72.2% of patients with cerebral vasospasm following subarachnoid hemorrhage and is most effective when the spasm is limited to peripheral vessels and the patient is younger and does not have a large cerebral infarction in the spasm artery perfusion area. [Read the Full Post]

Emergence of monkeypox: a worldwide public health crisis

86 | Feb 23 2023

Monkeypox, a zoonotic virus similar to smallpox that infects humans, has become a global health threat with growing incidence and geographic distribution, and currently lacks a specific therapy but can be treated with vaccines and FDA-approved antiviral medications such as brincidofovir, tecovirimat, and cidofovir. [Read the Full Post]

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT

129 | Feb 22 2023

In this study, results showed that TBI/Cy conditioning was associated with reduced risk of relapse and increased risk of grade 2-4 acute GVHD, while a matched-pair analysis revealed a reduced rate of relapse and no significant effect on other transplantation outcomes when compared to TBI/Flu, leading to the conclusion that TBI/Cy should be considered a preferable regimen for allo-HCT in adult patients with ALL in complete remission. [Read the Full Post]

Drug resistance dependent on allostery: A P-loop rigor Eg5 mutant exhibits resistance to allosteric inhibition by STLC

86 | Feb 20 2023

Resistance to Eg5 inhibitors, a potential target for cancer chemotherapy, was explored using the HCT116 cell line and found to arise from a dominant point mutation in the P-loop of the ATP binding domain of Eg5, Eg5(T107N), causing strong non-exchangeable binding to microtubules and resistance to loop-L5 binding inhibitors, but potentially overcome by inhibitors that bind to sites other than the loop-L5 binding site. [Read the Full Post]

Single-cell transcriptomics reveals the role of Macrophage-Naïve CD4 + T cell interaction in the immunosuppressive microenvironment of primary liver carcinoma

125 | Feb 20 2023

The study investigates the important interactions between immune cells and their targeting drugs in liver carcinoma using single-cell and bulk transcriptomic data, revealing the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma and identifying five predictive drugs that may help improve the immunosuppressive microenvironment and prevent immune evasion. [Read the Full Post]

Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent

153 | Feb 18 2023

Rigosertib, a dual PLK1 and PI3K inhibitor, showed dose- and time-dependent efficacy against 5 human tumor cell lines in vitro, with A549 cells being the most sensitive and U87-MG cells the most resistant, with p53 levels affecting the efficacy, making Rigosertib a potential antineoplastic agent against lung cancer in humans. [Read the Full Post]

PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation

140 | Feb 18 2023

Rigosertib, an anticancer agent under clinical trials, targets PLK1 and modulates ELAVL1/HuR-miR-122 signaling to effectively inhibit the proliferation of wild-type and sofosbuvir resistance-associated HCVs, suggesting it could be useful for treating HCV and HCV-associated diseases. [Read the Full Post]

Early identification of a 12-bp tandem duplication in TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK): Clinical characterization and response to bisphosphonate therapy

115 | Feb 15 2023

A young girl with early-onset deafness, progressive external tooth root resorption, and increased bone turnover due to a 12-bp duplication within exon 1 of TNFRSF11A was successfully treated with bisphosphonates, preventing further skeletal disease. [Read the Full Post]

The effects of neoadjuvant zoledronic acid in breast cancer patients: A meta-analysis of randomized controlled trials

141 | Feb 15 2023

Our study showed that adding Zoledronic acid (ZA) to neoadjuvant therapy for breast cancer did not improve the pathological complete response rate and resulted in worse mortality compared to the control group, but subgroup analysis revealed a potential benefit for postmenopausal women and patients with triple-negative BC, warranting further investigation. [Read the Full Post]

Inhibitors of One or More Cellular Aurora Kinases Impair the Replication of Herpes Simplex Virus 1 and Other DNA and RNA Viruses with Diverse Genomes and Life Cycles

111 | Feb 13 2023

Aurora kinase inhibitors were identified through a high-throughput cell-based assay as potent inhibitors of herpes simplex virus 1 (HSV-1) gene expression and replication, as well as reducing replication of other RNA and DNA viruses including vaccinia virus and mouse hepatitis virus, demonstrating that aurora kinases play a pivotal role in the life cycles of diverse viruses. [Read the Full Post]

Effect of Gubenyiliu formula II and its disassembled prescriptions on cell autophagy in breast cancer through PI3K/AKT/mTOR pathway

276 | Feb 12 2023

This study confirmed that GYII can effectively treat breast cancer by inhibiting the PI3K/AKT/mTOR signaling pathway-mediated autophagy, while QX and FZ have different effects on tumor growth and metastasis. [Read the Full Post]

Specific gene module pair-based target identification and drug discovery

346 | Feb 12 2023

A novel method called "gene module pair-based target identification (GMPTI)" was developed to predict the targets of new compounds using consensus gene modules extracted from transcriptional profiles induced by perturbagens of known targets, resulting in the discovery of novel inhibitors for three PI3K pathway proteins. [Read the Full Post]

Successful Treatment of Patient With Ewing Sarcoma in the Setting of Inherited Cholestatic Liver Disease

122 | Feb 12 2023

Treatment of Ewing sarcoma in a patient with PFIC1 presents a challenge due to the reliance of standard chemotherapy on intact hepatic metabolism, which results in prolonged lymphopenia and severe infectious complications in this patient. [Read the Full Post]

Effect of hyperthermia alone and in combination with anticancer drugs on the viability of P388 leukemic cells

118 | Feb 12 2023

Local tumor hyperthermia (42°C) for 1 hour with antineoplastic drugs Adriamycin, Vincristine, or 5-Fluorouracil showed synergistic cell killing action against P388 murine lymphocytic leukemia cells in vitro, while Cyclophosphamide and Cytosine Arabinoside did not show enhanced therapeutic effects. [Read the Full Post]

Zearalenone and its metabolite exposure directs oestrogen metabolism towards potentially carcinogenic metabolites in human breast cancer MCF-7 cells

131 | Feb 11 2023

Mycoestrogens increase the production of CYP1B1-mediated oestrogen catechol metabolites, directing the biotransformation of E2 towards 4-OHE2, a crucial factor in oestrogen-induced tumour initiation. [Read the Full Post]

Survival in a consecutive series of 467 glioblastoma patients: Association with prognostic factors and treatment at recurrence at two independent institutions

81 | Feb 11 2023

A study of 467 recurrent glioblastoma patients in Norway found that age, promoter methylation of MGMT, tumour location, and extent of resection at primary diagnosis were independent prognostic factors, while 60 Gray radiotherapy with concomitant and adjuvant temozolomide at primary diagnosis, gamma knife/stereotactic radiosurgery at first recurrence, and combination chemotherapy with or without bevacizumab at second recurrence were treatments associated with superior survival. [Read the Full Post]

Does PARP Inhibition Sensitize Chondrosarcoma Cell Lines to Chemotherapy or Radiotherapy? Results From a Three-dimensional Spheroid Cell Model

142 | Feb 11 2023

This study shows that long-term talazoparib treatment, a PARP inhibitor, effectively reduced the viability of three representative chondrosarcoma cell lines grown as spheroids, and the combination of talazoparib and temozolomide had a higher chance of success than combination with radiotherapy. [Read the Full Post]

Inhibition of multiple CDKs potentiates colon cancer chemotherapy via p73-mediated DR5 induction

91 | Feb 10 2023

CDK inhibitors sensitize colorectal cancer cells to therapy-induced apoptosis by inducing Death Receptor 5 via p73-mediated transcriptional activation, making p73-mediated DR5 induction a critical target engaged by CDKIs in potentiating therapy-induced apoptosis in colorectal cancer cells. [Read the Full Post]

Flavopiridol Protects against Fungal Keratitis due to Aspergillus fumigatus by Alleviating Inflammation through the Promotion of Autophagy

69 | Feb 10 2023

Flavopiridol reduces inflammation in fungal keratitis by promoting autophagy, phagocytosis, and antifungal activity, indicating its potential as a therapeutic option for fungal keratitis. [Read the Full Post]

Synthesis and antiproliferative activity evaluation of B-norcholesterol-6-amide compounds

132 | Feb 10 2023

The study found that introducing chloroalkyl acyl groups into the 6-position of 6-amino-B-norcholesterol greatly enhanced the cytotoxicity of the resulting B-norcholesterol-6-amide compounds, with compound 20 having an IC50 value of 3.9 μM on HeLa cells. [Read the Full Post]

Effect of Severe Renal Dysfunction on the Plasma Levels of DNA-Reactive Platinum after Oxaliplatin Administration

76 | Feb 09 2023

Severe renal dysfunction has a limited effect on the elimination rate of reactive DNA-binding platinum (fPt) in plasma after oxaliplatin administration, as shown by the results from studies in rats with bilateral nephrectomy and in a hemodialysis patient with advanced metastatic gastric cancer. [Read the Full Post]

A multi-center phase Ib study of oxaliplatin (NSC#266046) in combination with fluorouracil and leucovorin in pediatric patients with advanced solid tumors

122 | Feb 09 2023

The maximum planned dose of oxaliplatin in combination with 5-fluorouracil and leucovorin was safe and well tolerated in pediatric patients with refractory or relapsed solid tumors, with modest activity noted, warranting further study. [Read the Full Post]

Loss of tRNA methyltransferase 9 and DNA damage response genes in yeast confers sensitivity to aminoglycosides

147 | Feb 08 2023

The study showed that Trm9-catalyzed tRNA modifications enhance the DNA damage response and that cells with tRNA modification dysregulation and DNA repair gene defects can be selectively sensitized using a combination of translation inhibitors and DNA damaging agents. [Read the Full Post]

DNA radiosensitization by terpyridine-platinum: damage induced by 5 and 10 eV transient anions

64 | Feb 08 2023

Tpy-Pt enhances DNA damage induced by monoenergetic electrons in CRT, with the highest enhancement for base damage-related crosslinks, potentially causing roadblocks to replication and transcription in genomic DNA, particularly within telomeres where it binds preferentially to G-quadruplexes. [Read the Full Post]

Phase II Trials of Iniparib (BSI-201) in Combination with Gemcitabine and Carboplatin in Patients with Recurrent Ovarian Cancer

135 | Feb 08 2023

In two parallel phase II studies of iniparib (BSI-201) combined with gemcitabine and carboplatin in ovarian cancer patients, the overall response rate was 66% in platinum-sensitive disease and 26% in platinum-resistant disease, with higher response rates in patients with BRCA mutations and the combination was generally well tolerated with no new toxicities. [Read the Full Post]

Comparative study between two different morphological structures based on polylactic acid, nanocellulose and magnetite for co-delivery of flurouracil and curcumin

137 | Feb 07 2023

The magnetic copolymeric micelles M-PLA-co-NC/5-FU/CUR showed superior antibacterial and antitumor efficacy, slower release and higher loading % of CUR compared to the blended formulation PLA/M-NC/5-FU/CUR, making them a promising nanomedicine against bacteria and multiple cell lines. [Read the Full Post]

Extracellular vesicles derived from dental mesenchymal stem/stromal cells with gemcitabine as cargo have an inhibitory effect on the growth of pancreatic carcinoma cell lines in vitro

130 | Feb 07 2023

DP-MSC-EVs have therapeutic potential as a drug delivery tool for cancer therapy by absorbing and secreting gemcitabine and expressing a suicide gene to convert non-toxic prodrug 5-FC to cytotoxic drug 5-FU, resulting in significant inhibition of cancer cell growth. [Read the Full Post]

Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis

220 | Feb 07 2023

Gancao Nourishing-Yin decoction (GCNY) added to methotrexate (MTX) showed better effects in treating elderly rheumatoid arthritis (ERA) mice model compared to either treatment alone, as seen through improved joint damage, decreased inflammation, and regulation of metabolism-related pathways, and ELISAs confirmed improved folic acid levels and anti-folate resistance pathways. [Read the Full Post]

Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: a case-control study

155 | Feb 07 2023

The study found that ERA patients managed using a treat-to-target strategy had a similar incidence of cardiovascular events compared to a CV risk factor-matched non-RA population, while a historical RA cohort receiving routine care had a significantly higher incidence. [Read the Full Post]

CXCL9 links skin inflammation and fibrosis via CXCR3-dependent upregulation of collagen 1a1 in fibroblasts

97 | Feb 07 2023

The study provides evidence that CXCL9 and its receptor CXCR3 play a key role in the development of inflammation and fibrosis in morphea through the induction of collagen 1a1 expression. [Read the Full Post]

Novel carboxymethyl cellulose-halloysite-polyethylene glycol nanocomposite for improved 5-FU delivery

186 | Feb 06 2023

This study synthesized a pH-responsive nanocomposite based on halloysite nanotube (HNT) coated with carboxymethyl cellulose (CMC)/polyethylene glycol (PEG) hydrogel for controlled delivery of 5-Fluorouracil (5-FU), a hydrophobic chemotherapy drug, using the W/O/W technique, achieving high drug entrapment and loading and showing improved and sustained 5-FU delivery in acid environment and considerable cytotoxicity on MCF-7 breast cancer cells. [Read the Full Post]

The effect of cladribine on immunoglobulin levels compared to B cell targeting therapies in multiple sclerosis

140 | Feb 05 2023

Cladribine therapy for RRMS does not significantly reduce immunoglobulin subset levels, unlike ocrelizumab and natalizumab which showed a statistically significant reduction in IgG and IgM levels. [Read the Full Post]

Real-world experience of cladribine treatment in relapsing-remitting multiple sclerosis: A Danish nationwide study

140 | Feb 05 2023

A registry-based observational cohort study of all Danish patients starting cladribine tablets for relapsing multiple sclerosis showed the treatment was safe with a significant reduction in annualized relapse rate, but a longer follow-up period is needed to fully assess the long-term benefit and risk. [Read the Full Post]

In Vitro Characterization of 177Lu-DOTA-M5A Anti-Carcinoembryonic Antigen Humanized Antibody and HSP90 Inhibition for Potentiated Radioimmunotherapy of Colorectal Cancer

81 | Feb 02 2023

The combination therapy of 177Lu-radiolabeled anti-CEA hT84.66-M5A mAb (M5A) and the heat shock protein 90 inhibitor onalespib showed enhanced therapeutic effects over individual monotherapies for the potential treatment of colorectal cancer. [Read the Full Post]

Evaluating the role of polysaccharide extracted from Pleurotus columbinus on cisplatin-induced oxidative renal injury

117 | Feb 02 2023

The polysaccharide PsPc-3 from Pleurotus columbinus showed antioxidant activity and reduced oxidative renal injury induced by cisplatin in rats, indicating it may be a potential treatment for cisplatin-induced nephrotoxicity. [Read the Full Post]

Microglial P2Y12 Signaling Contributes to Cisplatin-induced Pain Hypersensitivity via IL-18-mediated Central Sensitization in the Spinal Cord

148 | Feb 02 2023

Microglia P2Y12-Src family kinase-p38 signaling contributes to cisplatin-induced pain hypersensitivity via IL-18-mediated central sensitization in the spinal cord, with P2Y12 being a potential target for preventing chemotherapy-induced pain hypersensitivity. [Read the Full Post]

Neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation for locally advanced cervical cancer

195 | Feb 01 2023

The study found that neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by concurrent chemoradiation was a feasible, safe and effective treatment for cervical cancer, with a high response rate and good overall survival. [Read the Full Post]

Preparation and evaluation of paclitaxel-loaded reactive oxygen species and glutathione redox-responsive poly(lactic-co-glycolic acid) nanoparticles for controlled release in tumor cells

150 | Feb 01 2023

The study found that PLGA copolymer with thioether and disulfide groups can effectively deliver paclitaxel to tumors, leading to increased drug accumulation at the site and offering a promising approach for intelligent and responsive drug delivery. [Read the Full Post]

Efficacy and safety of treatments for advanced thymic carcinoma after failure of first-line platinum-based chemotherapy: A systematic literature review and meta-analysis

151 | Feb 01 2023

This study conducted a systematic literature review of 19 clinical trials to assess the clinical outcomes of various regimens in patients with thymic carcinoma (TC) who failed first-line chemotherapy, finding limited treatment options with response rates ranging from 9% to 38% and prolonged duration of response with pembrolizumab, but a need for further well-powered clinical trials to better inform on optimal treatments. [Read the Full Post]

Upregulation of TGF-β-induced HSP27 by HSP90 inhibitors in osteoblasts

103 | Feb 01 2023

The study found that HSP90 inhibitors increased TGF-β-induced HSP27 expression in mouse osteoblastic MC3T3-E1 cells through the SAPK/JNK pathway. [Read the Full Post]

Lower SLC7A2 expression is associated with enhanced multidrug resistance, less immune infiltrates and worse prognosis of NSCLC

67 | Jan 31 2023

Shanshan Jiang et al. thought that SLC7A2 might act as a tumor suppressor to modulate drug sensitivity, immune infiltration and survival in NSCLC. [Read the Full Post]

Does neoadjuvant treatment in resectable pancreatic cancer improve overall survival? A systematic review and meta-analysis of randomized controlled trials

128 | Jan 31 2023

P L S Uson Junior et al. found that randomized ongoing trials were eagerly awaited with more active combined regimens including modified FOLFIRINOX. [Read the Full Post]

Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy

86 | Jan 30 2023

Zhengyuan Yu et al. suggested that LOC85009 might be a potential target to reverse DTX resistance in the treatment of LUAD. [Read the Full Post]

Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies

50 | Jan 30 2023

Niels A D Guchelaar et al. provided a systematic overview of intraperitoneal used drugs, the performed clinical studies so far, and the complications of the peritoneal implemental ports. [Read the Full Post]

SNS-023 sensitizes hepatocellular carcinoma to sorafenib by inducing degradation of cancer drivers SIX1 and RPS16

39 | Jan 29 2023

Yuan Liu et al. identified that both SIX1 and RPS16 were crucial substrates for the EGFR-AKT-USP1 axis-driven growth of HCC, suggesting a potential anti-HCC strategy from a novel perspective. [Read the Full Post]

Targeting aurora kinase B alleviates spinal microgliosis and neuropathic pain in a rat model of peripheral nerve injury

51 | Jan 29 2023

Yu Shen et al. indicated that AURKB played a critical role in spinal microgliosis and neuropathic pain. [Read the Full Post]

SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via inhibition of cyclin dependent kinase 9

39 | Jan 28 2023

Xiao-Li He et al. found that SNS-032 was a potential drug and CDK9 might be a new prospective target for the treatment of liver fibrosis. [Read the Full Post]

Rescue of Misfolded Organic Cation Transporter 3 Variants

134 | Jan 27 2023

Thomas J F Angenoorth et al. found that folding-deficient SLC22 transporter variants, in particular those of OCT3, were amenable to rescue by chaperones. [Read the Full Post]

Heat shock protein 90 inhibitors induce cell differentiation via the ubiquitin-dependent aurora kinase A degradation in a MPLW515L mouse model of primary myelofibrosis

75 | Jan 27 2023

Fuping Wang et al. demonstrated that combined therapy showed superior activity in acute megakaryocytic leukemia mouse model than single therapy. [Read the Full Post]

Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer

205 | Jan 26 2023

Akira Nakao et al. thought that the positivity of TTF-1 immunostaining in tumors could be a predominant prognostic marker for patients who had advanced nonsq NSCLC. [Read the Full Post]

Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma

242 | Jan 26 2023

Mi Jeong Hong et al. thought that two SNPs in miRNA binding sites, especially EXO1 rs1047840G>A, were associated with the chemotherapy response and survival outcome in lung adenocarcinoma patients treated with pemetrexed. [Read the Full Post]

Phenolipid JE improves metabolic profile and inhibits gluconeogenesis via modulating AKT-mediated insulin signaling in STZ-induced diabetic mice

119 | Jan 22 2023

Guihua Wang et al. suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway. [Read the Full Post]

Combination of palbociclib with navitoclax based-therapies enhances in vivo antitumoral activity in triple-negative breast cancer

99 | Jan 21 2023

Alejandra Estepa-Fernández et al. demonstrated that a combination treatment, using the senescence-inducer palbociclib and the senolytic agent navitoclax, delayed tumor growth. [Read the Full Post]

Upregulation of glutamate transporter 1 by mTOR/Akt pathway in astrocyte culture during oxygen-glucose deprivation and reoxygenation

103 | Jan 21 2023

Mi Li et al. suggested that astrocytes might adapt to short-term ischemic-reperfusion injury by regulating cell morphology, apoptosis and GLT-1 upregulation. [Read the Full Post]

β-Galactosidase-Activatable Nile Blue-Based NIR Senoprobe for the Real-Time Detection of Cellular Senescence

34 | Jan 20 2023

Beatriz Lozano-Torres et al. proved NBGal to be a qualitative, rapid, and minimally invasive probe that allowd the direct detection of senescent cells in vivo. [Read the Full Post]

Identifying the role of transient receptor potential channels (TRPs) in kidney renal clear cell carcinoma and their potential therapeutic significances using genomic and transcriptome analyses

95 | Jan 15 2023

Jie Ren et al. provided useful insight that could aid and guide clinical practice and scientific research. [Read the Full Post]

Construction and validation of a cuproptosis-related lncRNA signature as a novel and robust prognostic model for colon adenocarcinoma

128 | Jan 14 2023

Miaorong Xu et al. thought that a ten-cuproptosis-related lncRNA signature was constructed that provided promising insights into personalized prognosis and drug selection among COAD patients. [Read the Full Post]

Pharmacologic screen identifies active combinations with BET inhibitors and LRRK2 as a novel putative target in lymphoma

177 | Jan 13 2023

Filippo Spriano et al. identified combinations that could improve the response to BET inhibitors in lymphomas. [Read the Full Post]

A Novel Cuproptosis-Related Prognostic Model and the Hub Gene FDX1 Predict the Prognosis and Correlate with Immune Infiltration in Clear Cell Renal Cell Carcinoma

113 | Jan 07 2023

Kenan Zhang et al. constructed a CRGs prognostic model and revealed that FDX1 could serve as a prognostic biomarker and predict therapeutic response in ccRCC. [Read the Full Post]

Identification of cuproptosis-related long non-coding ribonucleic acid signature as a novel prognosis model for colon cancer

108 | Jan 07 2023

Rong Xu et al. found that inhibition of AL512306.3 and ZEB1-AS1 significantly suppressed the cell proliferation in colon cancer cells. [Read the Full Post]

Single-cell profiling reveals molecular basis of malignant phenotypes and tumor microenvironments in small bowel adenocarcinomas

142 | Jan 06 2023

Jingwei Yang et al. showed that the duodenal subtype of SBA exhibited molecular features more similar to gastric cancer whereas jejunal subtype of SBA more similar to colorectal cancer. [Read the Full Post]

Targeting integrated stress response with ISRIB combined with imatinib treatment attenuates RAS/RAF/MAPK and STAT5 signaling and eradicates chronic myeloid leukemia cells

117 | Dec 14 2022

Wioleta Dudka et al. proposed that personalized treatment based on the genetic selection of patients carrying mutations that caused overactivation of the targeted pathways. [Read the Full Post]

Novel biallelic mutations in TTC29 cause asthenoteratospermia and male infertility

64 | Dec 10 2022

Siyu Dai et al. found the novel biallelic mutations in TTC29 in a MMAF patient, which findings expand the mutational spectrum of TTC29. [Read the Full Post]

Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma

48 | Nov 18 2022

Liangming Zhang et al. found that EXO1 facilitated PD-L1 and sPD-L1 expression in LUAD cells. [Read the Full Post]

THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours

32 | Nov 15 2022

Jianyi Sun et al. demonstrated that CDK7 was relatively overexpressed in high-risk GISTs and predicted a poor outcome. [Read the Full Post]

Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers

0 | Nov 10 2022

Martin Gutierrez et al. found that the triplet combination of SNX-5422, carboplatin and paclitaxel followed by maintenance SNX-5422 therapy was well-tolerated and showed anti-tumor activity [Read the Full Post]

Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

0 | Nov 09 2022

Ria Goswami et al. found that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibited SARS-CoV-2 replication in vitro at a high selectivity index. [Read the Full Post]

Chk1 and the Host Cell DNA Damage Response as a Potential Antiviral Target in BK Polyomavirus Infection

0 | Nov 07 2022

Lydia E Hainley et al. thought that Chk1 inhibitors that were found to be safe and effective in clinical trials for cancer should be evaluated for antiviral activity against BKPyV. [Read the Full Post]

Four Chemotherapeutic Compounds That Limit Blood-Brain-Barrier Invasion by Toxoplasma gondii

29 | Nov 07 2022

Zijing Yan et al. Anxa1 was selected as the most appropriate material to prevent TE among four chemotherapeutic compounds closely related to C3. [Read the Full Post]

H3.3-G34 mutations impair DNA repair and promote cGAS/STING-mediated immune responses in pediatric high-grade glioma models

0 | Nov 05 2022

Santiago Haase et al. demonstrated that DDRi and STING agonists in combination with RT induce immune-mediated therapeutic efficacy in G34-mutant pHGG. [Read the Full Post]

Inhibiting PP2A Upregulates B7-H3 Expression and Potentially Increases the Sensitivity of Malignant Meningiomas to Immunotherapy by Proteomics

108 | Nov 02 2022

Boyi Hu et al. found that the PP2A inhibitor LB-100 increased the phosphorylation of STAT1 and B7-H3 expression, which could increase the sensitivity of malignant meningiomas to B7-H3 targeted immunotherapy. [Read the Full Post]

Ganetespib selectively sensitizes cancer cells for proximal and distal spread-out Bragg peak proton irradiation

152 | Oct 30 2022

Simon Deycmar et al. provided additional experimental data on cellular response and a rational for future combinatorial approaches with proton radiotherapy. [Read the Full Post]

Hsp90 Inhibitor STA9090 induced VPS35 related extracellular vesicle release and metastasis in hepatocellular carcinoma

98 | Oct 29 2022

Wenchong Tan et al. found that therapeutic strategy to inhibit the metastasis of HCC caused by N-terminal Hsp90 inhibitor induced extracellular vesicles. [Read the Full Post]

Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction

0 | Oct 25 2022

Gang Xie et al. suggested the potential value of PRT in managing osteolytic diseased mediated by osteoclasts. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

0 | Oct 25 2022

Ryo Kanamoto et al. found an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

UC-MSCs promote frozen-thawed ovaries angiogenesis via activation of the Wnt/β-catenin pathway in vitro ovarian culture system

137 | Oct 16 2022

Wenjuan Xu et al. showed the beneficial effects of UC-MSCs on thawed ovaries and explored a potential mechanism inducing angiogenesis. [Read the Full Post]

Treatment-related adverse events of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors in clinical trials: a meta-analysis

98 | Oct 16 2022

Ze Mi et al. thought that PD-L1 inhibitors plus CTLA-4 inhibitors showed better safety in treatment-related adverse events than PD-1 inhibitors plus CTLA-4 inhibitors. [Read the Full Post]

Vascular Disruptive Hydrogel Platform for Enhanced Chemotherapy and Anti-Angiogenesis through Alleviation of Immune Surveillance

72 | Oct 13 2022

Fasheng Li et al. provided a new treatment strategy through the mediation of the tumor immune microenvironment by vascular disruption to fulfill enhanced chemotherapy and immunotherapy. [Read the Full Post]

The Efficacy of Fosbretabulin Disodium Combined with Radiofrequency Ablation in Lung Cancer

52 | Oct 12 2022

Jieli Kou et al. found that FBTD promoted the antitumor effects of RFA in lung tumor-bearing mice in the study. [Read the Full Post]

Design, synthesis and biological evaluation of conformationnally-restricted analogues of E7010 as inhibitors of tubulin assembly (ITA) and vascular disrupting agents (VDA)

59 | Oct 12 2022

Vassili Prudhomme et al. found that indole 4j exhibited good potency against HUVEC and HIG-82 cell lines, as well as a good ability to inhibit tubulin assembly. [Read the Full Post]

A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer

84 | Oct 11 2022

Panagiotis A Konstantinopoulos et al. discovered that there was no obvious correlation with genomic alterations in responders vs non-responders, emphasizing the need for alternative biomarker approaches for responder identification. [Read the Full Post]

Simultaneous inhibition of Chk1 and Bcl-xL induces apoptosis in vitro and represses tumour growth in an in vivo xenograft model

53 | Oct 10 2022

Yoshihito Morimoto et al. suggested that the simultaneous inhibition of Chk1 and Bcl-xL might be an effective treatment for pancreatic cancer. [Read the Full Post]

Effects of Wee1 inhibitor adavosertib on patient-derived high-grade serous ovarian cancer cells are multiple and independent of homologous recombination status

127 | Oct 09 2022

Pia Roering et al. found that Wee1 inhibitor adavosertib affected several critical functions related to proliferation, cell cycle and division, apoptosis, and invasion. [Read the Full Post]

Cdk5 Promotes Mitochondrial Fission via Drp1 Phosphorylation at S616 in Chronic Ethanol Exposure-Induced Cognitive Impairment

36 | Sep 23 2022

Dandan Liu et al. demonstrated that inhibition of aberrant Cdk5 activation attenuates hippocampal neuron injury and cognitive deficits induced by chronic exposure to ethanol through Drp1-mediated mitochondrial fission and mitochondrial dysfunction. [Read the Full Post]

A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors

52 | Sep 22 2022

Stefano Di Giulio et al. highlighted the combination of PARP and CHK1 inhibitors as a new potential chemo-free strategy to treat MYCN-driven tumors, which might be promptly translated into clinical trials. [Read the Full Post]

Chk1 inhibition-induced BRCAness synergizes with olaparib in p53-deficient cancer cells

66 | Sep 21 2022

Yang Zhao et al. found that Chk1 inhibition could be effectively targeted and confer sensitivity to olaparib toward p53-deficient and HR-proficient cancers. [Read the Full Post]

Helicase-primase inhibitors from Medshine Discovery Inc. (WO2018/127207 and WO2020/007355) for the treatment of herpes simplex virus infections - structure proposal for Phaeno Therapeutics drug candidate HN0037

75 | Sep 19 2022

Christian Gege described the opportunities and limitations of the helicase-primase inhibitor patent portfolio from Phaeno Therapeutics. [Read the Full Post]

Comprehensive clinical and virological characterization of three cases of fulminant liver failure owing to HSV1 primary infection

45 | Sep 19 2022

Stephan Spahn et al. thought that ACV/HPI-combinations might offer new therapeutic options for HSV-induced ALF. [Read the Full Post]

[Correlation between low expression of Hsp90 protein in keratinocytes and the number of small extracellular vesicles and its potential clinical significance]

151 | Sep 17 2022

Jun Chen et al. found that the secretion of sEVs in HaCaT cells. sEVs may be involved in the transfer of molecules between epithelial cells and immune cells. [Read the Full Post]

Identification of potential immunotherapy biomarkers for breast cancer by bioinformatics analysis

153 | Sep 16 2022

Yao Song et al. found that CD24, MMP1, SDC1, and SPP1 were potentially associated with five immune cell types infiltration (CD8+ T cells, CD4+ T cells, neutrophils, macrophages,and dendritic cells) by TIMER. [Read the Full Post]

Dibutyl phthalate promotes angiogenesis in EA.hy926 cells through estrogen receptor-dependent activation of ERK1/2, PI3K-Akt, and NO signaling pathways

108 | Sep 15 2022

Dunja Kokai et al. found that DBP exerted a pro-angiogenic effect on human vascular ECs and described the molecular mechanism involving ER- and GPER-dependent activation of ERK1/2, PI3K-Akt, and NO signaling pathways. [Read the Full Post]

Repeated treatments of Capan-1 cells with PARP1 and Chk1 inhibitors promote drug resistance, migration and invasion

86 | Sep 06 2022

Ne Guo et al. found that activating CXCL3-ERK1/2 signaling might contribute to the enhanced migratory capabilities rather than the acquired drug resistance. [Read the Full Post]

Non-small cell lung cancer with EGFR exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes

156 | Sep 05 2022

Christina Soeun Kwon et al. found EGFR exon 20 insertion mutations as the availability of new targeted treatments might offer additional therapeutic options to these patients. [Read the Full Post]

A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922

146 | Sep 05 2022

Melissa Schwab et al. found that the membrane Hsp70 density, but not cytosolic HSP levels determined the radiosensitizing effect of the Hsp90 inhibitor NVP-AUY922 in LDH-/- cells. [Read the Full Post]

Design, synthesis, and biological evaluation of potent FAK-degrading PROTACs

136 | Sep 03 2022

Qiaohua Qin et al. found that PROTAC A13 could be useful as expand tool for studying functions of FAK in biological system and as potential therapeutic agents. [Read the Full Post]

Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against Toxoplasma gondii

117 | Aug 27 2022

Débora Chaves Cajazeiro et al. found that interactions with the Na+/K+ ATPase transporter for Homo sapiens and Mus musculus, indicating a possible mechanism of action of this compound. [Read the Full Post]

Radical S-Adenosyl Methionine Enzyme BlsE Catalyzes a Radical-Mediated 1,2-Diol Dehydration during the Biosynthesis of Blasticidin S

103 | Aug 26 2022

Yu-Hsuan Lee et al. suggested that BlsE catalysis likely proceeded via direct elimination of water from the CGA C4' α-hydroxyalkyl radical as opposed to 1,2-migration of the C3'-hydroxyl prior to dehydration. [Read the Full Post]

Phase I trial of ribociclib with platinum chemotherapy in recurrent ovarian cancer

46 | Aug 23 2022

Lan G Coffman et al. demonstrated the combination of ribociclib with chemotherapy in ovarian cancer was feasible and safe. [Read the Full Post]

In vitro and in vivo evaluation of kinase and protease inhibitors against Trypanosoma evansi

91 | Aug 21 2022

Wangchuk Dorjee Bhutia et al. showed that kinase inhibitors had higher potential to explore therapeutic molecules against surra organism. [Read the Full Post]

Discovery of Novel GMPS Inhibitors of Candidatus Liberibacter Asiaticus by Structure Based Design and Enzyme Kinetic

0 | Aug 21 2022

Jing Nan et al. suggested that folic acid and AZD1152 could be considered as promising candidates for the development of CLas agents. [Read the Full Post]

Casein Kinase 2 Signaling in White Matter Stroke

195 | Aug 04 2022

Hung Nguyen et al. thought that miRNA regulation might be one of the protective actions of CX-4945 against WM ischemic injury. [Read the Full Post]

Anti-adipogenic and Pro-lipolytic Effects on 3T3-L1 Preadipocytes by CX-4945, an Inhibitor of Casein Kinase 2

172 | Aug 04 2022

Anil Kumar Yadav et al. found that CX-4945 had strong anti-adipogenic and pro-lipolytic effects on differentiating and differentiated 3T3-L1 cells, mediated by control of the expression and phosphorylation levels of CK2, C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, AMPK, LKB-1, ERK-1/2, and HSL. [Read the Full Post]

Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy

266 | Jul 30 2022

Pincha Devage Sameera Madushan Fernando et al. found that hesperidin showed therapeutic potential against PM2.5-induced skin damage by mitigating excessive ROS accumulation, autophagy, and apoptosis. [Read the Full Post]

Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies

68 | Jul 29 2022

John Hilton et al. found toxicity was related to the CX-5461 chemotype, independent of G-quadruplex synthetic lethality. [Read the Full Post]

Construction of m6A-Related lncRNA Prognostic Signature Model and Immunomodulatory Effect in Glioblastoma Multiforme

178 | Jul 22 2022

Pan Xie et al. constructed an m6A-associated lncRNA risk model to predict the prognosis of GBM patients and provided new ideas for the treatment of GBM. [Read the Full Post]

Metastatic pulmonary carcinoids with EML4-ALK fusion response to ALK inhibitors: two case reports and review of literature

225 | Jul 18 2022

Xi Lei et al. recommend alectinib for the first-line treatment of metastatic PC with EML4-ALK fusion. [Read the Full Post]

Simulating Colorectal Cancer Trials Using Real-World Data

199 | Jul 18 2022

Zhaoyi Chen et al. simulated five CRC trials, and tested two simulation scenarios with several different configurations demonstrated that our simulations couldrobustly generated effectiveness and safety outcomes comparable with the original trials using real-world data. [Read the Full Post]

Wee1 kinase inhibitor adavosertib with radiation in newly diagnosed diffuse intrinsic pontine glioma: A Children's Oncology Group phase I consortium study

91 | Jul 14 2022

Sabine Mueller et al. found that adavosertib in combination with CRT was well tolerated in children with newly diagnosed DIPG, however, compared to historical controls, did not improve OS. [Read the Full Post]

Shedding light on the binding mechanism of kinase inhibitors BI-2536, Volasetib and Ro-3280 with their pharmacological target PLK1

103 | Jul 08 2022

Jesús Fernández-Sainz et al. thought that the higher affinity of the inhibitors to PLK1 compared to ATP was mainly attributed to stronger van der Waals interactions. [Read the Full Post]

PLK inhibitors identified by high content phenotypic screening promote maturation of human PSC-derived cardiomyocytes

108 | Jul 07 2022

Mengying Feng et al. found that PLK inhibitors could promote maturation of hPSC-CMs through suppressing AKT signaling pathway. [Read the Full Post]

Efficacy, safety and toxicity management of adjuvant abemaciclib in early stage HR+/HER2- high-risk breast cancer

69 | Jun 28 2022

Sarah Sammons et al. discussed the data, the population studied and the population in which abemaciclib was approved as well as safety, tolerability, and dose reductions for practical management of these patients. [Read the Full Post]

Aurora kinase a inhibitor MLN8237 suppresses pancreatic cancer growth

201 | Jun 15 2022

Yuebo Zhang et al. provided the molecular basis for a novel chemotherapy strategy for PDAC patients. [Read the Full Post]

Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor

196 | Jun 14 2022

Santhosh A Upadhyaya et al. discovered that single agent alisertib was well tolerated by children with recurrent AT/RT, and SD or PR was observed in approximately a third of the patients. [Read the Full Post]

ARHGAP9 inhibits colorectal cancer cell proliferation, invasion and EMT via targeting PI3K/AKT/mTOR signaling pathway

474 | Jun 10 2022

Jufeng Sun et al. thought that ARHGAP9 inhibited the malignant phenotypes of CRC cells via interdicting PI3K/AKT/mTOR signaling pathway. [Read the Full Post]

Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis

188 | Jun 09 2022

Md Parvez Mosharaf et al. validated six FDA-approved launched drugs (Dinaciclib, Afatinib, Icotinib, Bosutinib, Dasatinib, and TWS-119) by molecular docking interaction analysis with the respective target proteins for the treatment against NSCLC. [Read the Full Post]

Inhibitory Response to CK II Inhibitor Silmitasertib and CDKs Inhibitor Dinaciclib Is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines

158 | Jun 09 2022

Yixuan Ma et al. thought that specific aberrations in TP53 and KRAS affected the efficacy of both inhibitors. [Read the Full Post]

Lonafarnib Inhibits Farnesyltransferase via Suppressing ERK Signaling Pathway to Prevent Osteoclastogenesis in Titanium Particle-Induced Osteolysis

240 | Jun 07 2022

Linke Huang et al. found that Lon was a promising treatment option for osteoclast-related osteolysis diseases including periprosthetic osteolysis by targeted inhibition of FTase through suppressing ERK signaling. [Read the Full Post]

Successful treatment with steroid pulse therapy for a COVID-19 case with progressive respiratory failure during treatment for pleural metastasis of breast cancer

111 | May 18 2022

Hikari Jimbo et al. thought that a critical element in cases such as this one was that treatment decisions were made by a team of specialists, including pulmonologists. [Read the Full Post]

ARHGAP29 Regulates Keratinocyte Migration through the RhoA/ROCK Pathway

278 | May 15 2022

Lindsey Rhea et al. demonstrated that ARHGAP29 regulated keratinocyte morphology and promoted migration speed and directionality through the RhoA/ROCK pathway, providing potential insight into its importance in craniofacial development. [Read the Full Post]

Inside the cracked kernel: establishing the molecular basis of AMG510 and MRTX849 in destabilising KRASG12C mutant switch I and II in cancer treatment

280 | May 14 2022

Abdul Rashid Issahaku et al. found that these insights present useful atomistic perspectives into the success of AMG510 and MRTX849 which could guide the design of more selective and potent KRAS inhibitors.Communicated by Ramaswamy H. Sarma. [Read the Full Post]

COVID-19: Implications Regarding the Properties and Behaviors of the Coronavirus Disease

222 | May 14 2022

COVID-19 may be inaccurate due to errors in diagnosing and reporting, since other similar illnesses may exhibit similar symptoms. [Read the Full Post]

Non-cytomembrane PD-L1: An atypical target for cancer

281 | May 12 2022

Honggang Ying et at. highlighted that non-cytomembrane PD-L1s were of significant cancer diagnostic value and were promising therapeutic targets to treat cancer. [Read the Full Post]

Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two F508del Alleles

242 | May 12 2022

Simon Y Graeber et al. found that improvement of CFTR function by ELX/TEZ/IVA improved lung ventilation and abnormalities in lung morphology including airway mucus plugging and wall thickening in adolescent. [Read the Full Post]

Efficacy of sirolimus in children with lymphatic malformations of the head and neck

145 | May 09 2022

S Wiegand 1 et al. found that sirolimus could be an effective treatment for children with large complicated lymphatic malformations of the head and neck. [Read the Full Post]

Inhibitors of the Ubiquitin Proteasome System block myofibril assembly in cardiomyocytes derived from chick embryos and human pluripotent stem cells

235 | May 05 2022

Jushuo Wang et al. suggested a possible explanation for the cardiac and skeletal muscle off-target effects reported in multiple myeloma patients treated with proteasome inhibitors. [Read the Full Post]

Utilizing Three-Dimensional Culture Methods to Improve High-Throughput Drug Screening in Anaplastic Thyroid Carcinoma

256 | Apr 29 2022

Kensey Bergdorf et al. utilized three-dimensional culture methods, as they had been shown to more accurately recapitulate tumor responses in vivo. [Read the Full Post]

Treatment of a Double Cancer Patient With Primary Inferior Vena Cava Sarcoma and Lung Adenocarcinoma: A Case Report and Literature Review

241 | Apr 26 2022

Xiaohu Guo et al. found that surgery was still an effective treatment for patients with a primary IVC leiomyosarcoma and lung adenocarcinoma at present. [Read the Full Post]

Phase II Clinical and Translational Study of Everolimus ± Paclitaxel as First-Line Therapy in Cisplatin-Ineligible Advanced Urothelial Carcinoma

294 | Apr 25 2022

Tomi Jun et al. thought that everolimus plus paclitaxel demonstrated clinical activity in cisplatin-ineligible patients with metastatic UC, although the specific contribution of everolimus could not be delineated. [Read the Full Post]

First-line therapy in non-small cell lung cancer patients with EGFR activating mutations: a consideration of the clinical position of osimertinib based on the subset of Japanese patients in the FLAURA study

260 | Apr 22 2022

Yoko Tsukita et al. reviewed data from the randomized clinical trials of first-line EGFR-TKIs including a subset of Japanese patients and discussed first-line therapies for patients with NSCLC harbouring EGFR mutations. [Read the Full Post]

Novel immune-related signature based on immune cells for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma

124 | Apr 21 2022

Libin Zhou et al.defined a robust signature that might be promising for predicting clinical outcomes and immunotherapy and targeted therapy response in ccRCC patients. [Read the Full Post]

Diet impacts triple-negative breast cancer growth, metastatic potential, chemotherapy responsiveness, and doxorubicin-mediated cardiac dysfunction

314 | Apr 20 2022

Manuel U Ramirez et al. found that the Mediterranean diet might reduce lung metastatic lesions formation and prevent the development of cardiac toxicities. [Read the Full Post]

Partial response to dabrafenib and trametinib in relapsed BRAF V600E-Mutated multiple myeloma and possible mechanisms of resistance

177 | Apr 18 2022

Tina Ernst et al. described a very good partial response and possible mechanisms of resistance to a combination of the BRAF inhibitor dabrafenib. [Read the Full Post]

Multiple myeloma: Combination therapy of BET proteolysis targeting chimeric molecule with CDK9 inhibitor

0 | Apr 14 2022

Su-Lin Lim et al. found that the combination of a BET PROTAC (ARV 825) plus AZD 4573 (CDK9 inhibitor) was effective against MM cells. [Read the Full Post]

Inhibition of CDK9 attenuates atherosclerosis by inhibiting inflammation and phenotypic switching of vascular smooth muscle cells

158 | Apr 04 2022

Shushi Huang et al. found that inhibition of CDK9 might be a novel therapeutic target for the prevention of atherosclerosis. [Read the Full Post]

Factors Influencing the Intracellular Concentrations of the Sofosbuvir Metabolite GS-331007 (in PBMCs) at 30 Days of Therapy

349 | Apr 02 2022

Jessica Cusato et al. presented data on an IC evaluation in a cohort of patients treated with SOF, also considering pharmacogenetics. [Read the Full Post]

In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells

463 | Apr 01 2022

Alessio Malacrida et al. thought that rigosertib could be a potential therapeutic option, alone or in combination with radiations, for nonresectable patients with cholangiocarcinoma. [Read the Full Post]

Drug repurposing through virtual screening and in vitro validation identifies tigecycline as a novel putative HCV polymerase inhibitor

328 | Apr 01 2022

Mahmoud ElHefnawi et al. found that tigecycline displayed synergistic activity with sofosbuvir and daclatasvir against HCV. [Read the Full Post]

Rigosertib and Cholangiocarcinoma: A Cell Cycle Affair

406 | Mar 31 2022

Alessio Malacrida et al. hypothesized the mechanism of the action of Rigosertib against cholangiocarcinoma EGI-1 cells, highlighting the importance of proteins involved in the regulation of cell cycles. [Read the Full Post]

Response to netarsudil in goniotomy-treated eyes and goniotomy-naïve eyes: a pilot study

658 | Mar 29 2022

Haochen Xu et al.showed that netarsudil had a greater IOP-lowering effect in eyes treated with prior goniotomy and might serve as a promising adjunctive ocular hypotensive agent to further reduce IOP in eyes with prior goniotomy. [Read the Full Post]

Cyclin-dependent kinase 7/9 inhibitor SNS-032 induces apoptosis in diffuse large B-cell lymphoma cells

218 | Mar 29 2022

Liling Jiang et al. provided pre-clinical evidence for application of targeting the CDK7/9 in DLBCL. [Read the Full Post]

CDK4/6 inhibition synergizes with inhibition of P21-Activated Kinases (PAKs) in lung cancer cell lines

235 | Mar 28 2022

Gabriela M Wright et al. suggested that a unique combination of PAKs played a crucial role in the synergy of PAK inhibitors with CDK4/6i. [Read the Full Post]

Defining Endocytic Pathways of Fucoidan-Coated PIBCA Nanoparticles from the Design of their Surface Architecture

700 | Mar 19 2022

M C B Lira-Nogueira et al. found that internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. [Read the Full Post]

The beneficial effect of salubrinal on neuroinflammation and neuronal loss in intranigral LPS-induced hemi-Parkinson disease model in rats

505 | Mar 18 2022

Fatma Nihan Cankara et al. found that salubrinal was attenuating several inflammatory mediators and thereby decreased the inflammatory effects of LPS in the neurons of the SN. [Read the Full Post]

Tumorigenic circulating tumor cells from xenograft mouse models of non-metastatic NSCLC patients reveal distinct single cell heterogeneity and drug responses

254 | Mar 15 2022

Kanve N Suvilesh et al. showed that CDX models deserved further development and studied to discover personalized strategies against micrometastases in non-metastatic NSCLC patients. [Read the Full Post]

The role of drug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP) and OATP1A/1B and of CYP3A4 in the pharmacokinetics of the CDK inhibitor milciclib

234 | Mar 14 2022

Alejandra Martínez-Chávez et al. found that the low impact of OATP1 and CYP3A could be clinically favorable for milciclib, reducing the risks of unintended drug-drug interactions or interindividual variation in CYP3A4 activity. [Read the Full Post]

A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells

0 | Mar 14 2022

Chiara Ghezzi et al. thought that CDK7 was a key regulator of glucose consumption in cells with an activated PI3K pathway. [Read the Full Post]

Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes

225 | Mar 12 2022

Kathryn Davidson et al. had identified a novel drug tool with significant preclinical characterisation that served as an excellent candidate to explore and define LIMD1-deficient cancers as a new therapeutic subgroup of critical unmet need. [Read the Full Post]

The effect of danusertib, an Aurora kinase inhibitor, onto the cytotoxicity, cell cycle and apoptosis in pancreatic ductal adenocarcinoma cells

779 | Mar 11 2022

Ismail Ayberk Kirbiyik et al. thought that Aurora kinase inhibitor danusertib might be a potential alternative to the treatment of pancreatic cancers. [Read the Full Post]

Combined Inhibition of Polo-Like Kinase-1 and Wee1 as a New Therapeutic Strategy to Induce Apoptotic Cell Death in Neoplastic Mast Cells

758 | Mar 10 2022

Manuela Mancini et al. showed that repurposing Plk1 or AKA ± Wee1 inhibitors in advanced clinical development for other indications was a therapeutic strategy worthy of being explored, in order to improve the outcome of patients with advanced SM. [Read the Full Post]

Inhibition MNK-eIF4E-β-catenin preferentially sensitizes gastric cancer to chemotherapy

655 | Feb 25 2022

Xiaolin Yang et al. provided preclinical evidence to initialize clinical trials for gastric cancer using tomivosertib in combination with chemotherapy. [Read the Full Post]

Functional Assessment of Kinesin-7 CENP-E in Spermatocytes using In Vivo Inhibition, Immunofluorescence and Flow Cytometry

338 | Feb 24 2022

Meng-Fei Xu et al. found that CENP-E inhibition resulted in chromosome misalignment and metaphase arrest in primary spermatocytes during meiosis I. [Read the Full Post]

Predictors of Treatment Response and Long-Term Outcomes in Young Children with Steroid-Dependent Nephrotic Syndrome Treated with High-Dose Mizoribine as First-Line Steroid-Sparing Agent

366 | Feb 23 2022

Shuichiro Fujinaga et al. discovered that high-dose mizoribine might be an attractive treatment option as initial SSA in young children with low steroid-dependent dose for improved long-term outcomes. [Read the Full Post]

Epigenetic and Immune-Cell Infiltration Changes in the Tumor Microenvironment in Hepatocellular Carcinoma

171 | Feb 22 2022

Zeng-Hong Wu et al. showed that epigenetic-related novel biomarkers could be useful in predicting prognosis, clinical diagnosis, and management in HCC. [Read the Full Post]

The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction

462 | Feb 14 2022

Casandra Gomez-Paredes et al. found that following pharmacological activation in vivo,the heat shock response impairment in tibialis anterior, brain hemispheres and striatum was comparable between zQ175 and R6/2 mice. [Read the Full Post]

Osthole Exerts Inhibitory Effects on Hypoxic Colon Cancer Cells via EIF2[Formula: see text] Phosphorylation-mediated Apoptosis and Regulation of HIF-1[Formula: see text]

307 | Feb 13 2022

Kui-Yuan Peng et al. thought that osthole might be a potential agent in the treatment of colon cancer. [Read the Full Post]

Drug-repurposing against COVID-19 by targeting a key signaling pathway: An in silico study

453 | Feb 13 2022

Ki Kwang Oh et al. provided three key elements to alleviate COVID-19 symptoms might be anti-inflammatory effects on SARs-CoV-2-infected lung cells. [Read the Full Post]

Role of KSP inhibitors as anti-cancer therapeutics: an update

415 | Feb 06 2022

Rinkal Chamariya et al. thought that KSP inhibitors had exhibited promising results and continued exploration was greatly required to establish the clinical potential of KSP inhibitors. [Read the Full Post]

Efficacy and Synergy of Small Molecule Inhibitors Targeting FLT3-ITD + Acute Myeloid Leukemia

397 | Feb 06 2022

Javier Bregante et al. suggested WS6, ispinesib, ponatinib and cabozantinib as novel options for targeting FLT3-ITD+ AML. [Read the Full Post]

A Novel Role for the Regulatory Nod-Like Receptor NLRP12 in Anti-Dengue Virus Response

416 | Jan 28 2022

Xingyu Li et al. demonstrated a novel mechanism that NLRP12 exerted anti-viral properties in DENV and other flaviviruses (JEV, YFV, ZIKV) infection. [Read the Full Post]

The main difference between Alvespimycin vs. 17-DMAG. Biomimetic Platform Based on Mesoporous Platinum for Multisynergistic Cancer Therapy

431 | Jan 27 2022

Gaoqian Zhao et al. showed that 17-DMAG/MPNPs@PM could accumulate in the tumor and effectively inhibit the growth of tumor cells. [Read the Full Post]

Drug repositioning based on gene expression data for human HER2-positive breast cancer

410 | Jan 21 2022

Farkhondeh Khanjani et al. suggested that some repurposed drugs based on gene expression data could be noticed as potential drugs for the treatment of HER2-positive breast cancer. [Read the Full Post]

Integrated Genomic Profiling and Drug Screening of Patient-Derived Cultures Identifies Individualized Copy Number-Dependent Susceptibilities Involving PI3K Pathway and 17q Genes in Neuroblastoma

258 | Jan 20 2022

Rachel L Y Wong et al. defined individualized dose-dependent relationships between copy number gains of PI3K and STAT family genes particularly on 17q and susceptibility to PI3K and cell cycle agents in neuroblastoma. [Read the Full Post]

Regulation of the mammalian maternal-to-embryonic transition by eukaryotic translation initiation factor 4E

614 | Jan 18 2022

Yan Li et al. thought that eIF4E activity was regulated at key embryonic transitions in the mammalian embryo and was essential for the successful transition from maternal to embryonic control of development. [Read the Full Post]

Single cell transcriptomic profiling of neurodegeneration mediated by tau in a novel 3D neuron-astrocyte coculture model

429 | Jan 14 2022

Hannah Rickner et al. demonstrated the power to model the reduction of tau pathology by drug treatment. [Read the Full Post]

Proliferation of bovine endometrial epithelial cells is promoted by prostaglandin E 2-PTGER2 signaling through cell cycle regulation

227 | Dec 26 2021

Bo Liu et al. demonstrated that PGE2-PTGER2 signaling activation had a direct molecular association with cell cycle regulation and cell proliferation in bEECs. [Read the Full Post]

Identification of CDK7 Inhibitors from Natural Sources Using Pharmacoinformatics and Molecular Dynamics Simulations

162 | Dec 22 2021

Vikas Kumar et al. argued that proposed hits might be crucial against CDK7-related malignancies. [Read the Full Post]

Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers

565 | Dec 17 2021

Martin Gutierrez et al. found that the triplet combination of SNX-5422, carboplatin and paclitaxel followed by maintenance SNX-5422 therapy was well-tolerated and showed anti-tumor activity. [Read the Full Post]

Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

525 | Dec 16 2021

Ria Goswami et al. found that SNX-5422 interrupted expression of host factors demonstrated to be crucial for SARS-CoV-2 replication. [Read the Full Post]

Chk1 and the Host Cell DNA Damage Response as a Potential Antiviral Target in BK Polyomavirus Infection

406 | Dec 14 2021

Lydia E Hainley et al. found that Chk1 inhibitors were safe and effective in clinical trials for cancer should also be evaluated for antiviral activity against BKPyV. [Read the Full Post]

In silico identification and characterization of small-molecule inhibitors specific to RhoG/Rac1 signaling pathway

228 | Dec 14 2021

Pankaj Dipankar et al. indicated that Rac1 inhibitors had the potential for use as therapeutics in conditions involving dysregulation of RhoG.Communicated by Ramaswamy H. Sarma. [Read the Full Post]

Synergistic cytotoxicity of the CDK4 inhibitor Fascaplysin in combination with EGFR inhibitor Afatinib against Non-small Cell Lung Cancer

223 | Dec 12 2021

Adelina Plangger et al. showed high cytotoxicity against pleural primary NSCLC lines that could be further boosted when combined with the EGFR TKI afatinib. [Read the Full Post]

Activation of Yes-Associated Protein/PDZ-Binding Motif Pathway Contributes to Endothelial Dysfunction and Vascular Inflammation in AngiotensinII Hypertension

503 | Dec 08 2021

Qian Xu et al. suggested that AngII induced YAP/TAZ activation via PP2A-dependent dephosphorylation, which might contribute to the impairment of endothelial function and the induction of vascular inflammation in hypertension. [Read the Full Post]

HSP90 inhibition downregulates DNA replication and repair genes via E2F1 repression

671 | Dec 05 2021

Hanqing Liu et al. found that HSP90 inhibitors might be useful in combination therapies for MCL. [Read the Full Post]

Investigation of anticancer activities of STA-9090 (ganetespib) as a second generation HSP90 inhibitor in Saos-2 osteosarcoma cells

643 | Dec 05 2021

Aykut Özgür found the down-regulation of the expression levels of oncogenic genes. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

0 | Dec 01 2021

Ryo Kanamoto et al. found an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction

924 | Nov 30 2021

Gang Xie et al. suggested the potential value of PRT in managing osteolytic diseases mediated by osteoclasts. [Read the Full Post]

First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small cell lung cancer

373 | Nov 22 2021

J Niu et al. found that vibostolimab plus pembrolizumab was well tolerated and demonstrated antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC. [Read the Full Post]

Mutual regulation between chicken telomerase reverse transcriptase and the Wnt/β-catenin signalling pathway inhibits apoptosis and promotes the replication of ALV-J in LMH cells

652 | Nov 21 2021

Yong Xiang et al. found that chTERT not only shortened the cell cycle to promote proliferation but also inhibited apoptosis by downregulating the expression of Caspase 3, Caspase 9 and BAX. [Read the Full Post]

Multimodal obstruction of tumorigenic energy supply via bionic nanocarriers for effective tumor therapy

408 | Nov 19 2021

Xiaoqian Yu et al. found that the CA4P/VK2-MSNs-TBAM/TSAG-HA (CVMMGH for short) nanocarrier combined well-controllable manipulation of tumor vasculature and tumor mitochondria to effectivly cut off the tumorigenic energy supply. [Read the Full Post]

A high-throughput and simultaneous determination of combretastatin A-4 phosphate and its metabolites in human plasma using HPLC-MS/MS: Application to a clinical pharmacokinetic study

384 | Nov 18 2021

Qizhen Wu et al. thought that an abundant ammonium adduct ion of CA4G in ESI+ was observed as an ideal precursor ion. [Read the Full Post]

Sequential drug delivery by injectable macroporous hydrogels for combined photodynamic-chemotherapy

389 | Nov 18 2021

Yuanyuan Zhong et al. found that dual drugs treated groups had better tumor inhibition than solo drug under near infrared laser irradiation [Read the Full Post]

Chk1 inhibition potently blocks STAT3 tyrosine705 phosphorylation, DNA binding activity, and activation of downstream targets in human multiple myeloma cells

242 | Nov 17 2021

Liang Zhou et al. suggest that Chk1 pathway inhibitors warranted attention as novel and potent candidate STAT3 antagonists in myeloma. [Read the Full Post]

A Phase 1b Trial of Prexasertib in Combination with Standard-of-Care Agents in Advanced or Metastatic Cancer

331 | Nov 17 2021

Kathleen N Moore et al. found that prexasertib could be combined with cisplatin, cetuximab, and 5-fluorouracil. [Read the Full Post]

Evidence of Rate Limiting Proton Transfer in an S N Ar Aminolysis in Acetonitrile under Synthetically Relevant Conditions

253 | Nov 15 2021

Ian W Ashworth et al. found that 1-methylpiperazine, and the piperazine derived impurity correlated in a Brønsted type analysis with the pKa's (acetonitrile) of the amine nucleophile. [Read the Full Post]

Discovery of novel quinazoline-based covalent inhibitors of KRAS G12C with various cysteine-targeting warheads as potential anticancer agents

480 | Nov 13 2021

Ling Li et.al suggested that the novel covalent inhibitors of KRAS G12C with different warheads deserve further investigation as potential anticancer agents. [Read the Full Post]

The cyclin dependent kinase inhibitor Roscovitine prevents diet-induced metabolic disruption in obese mice

229 | Nov 02 2021

Nabil Rabhi et al. concluded that roscovitine was effective at preventing prolonged diet-induced metabolic disruption and restoring mitochondrial activity in BAT and eWAT. [Read the Full Post]

Suppression of ventricular arrhythmias by targeting late L-type Ca2+ current

208 | Nov 02 2021

Marina Angelini et al. supported the value of an antiarrhythmic strategy based on the selective reduction of late ICa,L to suppress EAD-mediated arrhythmias. [Read the Full Post]

A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors

282 | Oct 31 2021

Stefano Di Giulio et al. found the combination of PARP and CHK1 inhibitors as a new potential chemo-free strategy to treat MYCN-driven tumors, which might be promptly translated into clinical trials. [Read the Full Post]

Radiation-Induced Autophagy in Human Pancreatic Cancer Cells is Critically Dependent on G2 Checkpoint Activation: A Mechanism of Radioresistance in Pancreatic Cancer

287 | Oct 31 2021

Motofumi Suzuki et al. found that Biological crosstalk existed between the G2 checkpoint activation and radiation-induced autophagy processes. [Read the Full Post]

Discovering potential inhibitors against SARS-CoV-2 by targeting Nsp13 Helicase

397 | Oct 28 2021

Rajat Nandi et al. suggested that pritelivir might work as viable therapeutics for efficient drug advancement against SARS-CoV-2 Nsp13 helicase, potentially arresting the SARS-CoV-2 replication. [Read the Full Post]

Novel Cost-Efficient Graphene-Based Impedance Biosensor for the Analysis of Viral Cytopathogenicity and the Effect of Antiviral Drugs

326 | Oct 28 2021

Anke Schultz et al. found the suitability of the printed graphene biosensors for impedance-based monitoring of viral cytopathogenicity and its inhibition in the presence of antiviral drugs. [Read the Full Post]

Co-Expression of CD34, CD90, OV-6 and Cell-Surface Vimentin Defines Cancer Stem Cells of Hepatoblastoma, Which Are Affected by Hsp90 Inhibitor 17-AAG

753 | Oct 26 2021

Mieun Lee-Theilen et al. identified CSCs of hepatoblastoma using CD34, CD90, OV-6 and csVimentin. [Read the Full Post]

Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma

829 | Oct 25 2021

Yi He et al. highlighted the potential pathogenesis of the circRNA-miRNA-mRNA regulatory network and identified novel therapeutic options for glioma. [Read the Full Post]

Ceramide modulates electrophysiological characteristics and oxidative stress of pulmonary vein cardiomyocytes

795 | Oct 24 2021

Shih-Yu Huang et al. thought that C2 ceramide might exert the distinctive electrophysiological effect of modulating PV activities. [Read the Full Post]

Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

0 | Oct 22 2021

E M Samoilova et al. thought that reprogramming with small molecules without additional factors modifying gene expression did not allow reproducible production of human neural stem cell-like progenitors that could be used as the source of neural tissue for the regenerative therapy. [Read the Full Post]

HSP90 inhibition acts synergistically with heat to induce a pro-immunogenic form of cell death in colon cancer cells

1065 | Oct 14 2021

Petros X E Mouratidis et al. found that sub-ablative heating could act synergistically with the clinically relevant HSP90 inhibitor NVP-AUY922 to induce a pro-immunogenic form of cell death in colon cancer cells. [Read the Full Post]

CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin

411 | Oct 14 2021

Simone Di Franco et al. found that synergistic combination of NORA234 and CHK1 (rabusertib) targeting was synthetic lethal inducing death of both CD44v6-negative and CD44v6-positive CRC stem cell fractions, aside from Wnt pathway activity. [Read the Full Post]

Evolution of kinase polypharmacology across HSP90 drug discovery

1051 | Oct 13 2021

Albert A Antolin et al. found that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, displayed unique off-target kinase pharmacology as compared with other HSP90 inhibitors. [Read the Full Post]

Synthesis and evaluation of FAK inhibitors with a 5-fluoro-7H-pyrrolo[2,3-d]pyrimidine scaffold as anti-hepatocellular carcinoma agents

803 | Oct 12 2021

Hanyi Tan et al. suggested that 16c inhibited the malignant proliferation of hepatocellular carcinoma (HCC) cells through decreasing the phosphorylation in the FAK cascade. [Read the Full Post]

Successful treatment of hepatosplenic T-cell lymphoma with fludarabine, high-dose cytarabine and subsequent unrelated umbilical cord blood transplantation

721 | Oct 04 2021

Takaya Honda et al. found a heterozygous nonsense c.2961C>G (p.Tyr987Ter) variant of the KMT2C gene. [Read the Full Post]

A [3Fe-4S] cluster and tRNA-dependent aminoacyltransferase BlsK in the biosynthesis of Blasticidin S

674 | Oct 03 2021

Xiankun Wang et al. provided an example of an iron-sulfur protein that catalyzed an aminoacyl-tRNA (aa-tRNA)-dependent amide bond formation in a natural product biosynthetic pathway. [Read the Full Post]

Neoadjuvant Therapy of Cyclin-Dependent Kinase 4/6 Inhibitors Combined with Endocrine Therapy in HR+/HER2- Breast Cancer: A Systematic Review and Meta-Analysis

227 | Sep 29 2021

Kai Hong et al. suggested that combination therapy had increased efficacy and toxicity compared to endocrine monotherapy and showed similar efficacy to and better safety than neoadjuvant chemotherapy. [Read the Full Post]

Inhibition of Aurora Kinase B activity disrupts development and differentiation of salivary glands

453 | Sep 27 2021

Abeer K Shaalan et al. found AURKB as a key molecule in supporting embryonic development and differentiation, while inhibiting senescence-inducing signals during organogenesis. [Read the Full Post]

Discovery of Novel GMPS Inhibitors of Candidatus Liberibacter Asiaticus by Structure Based Design and Enzyme Kinetic

501 | Sep 27 2021

Jing Nan et al. suggested that folic acid and AZD1152 could be considered as promising candidates for the development of CLas agents. [Read the Full Post]

Small Molecule "Silmitasertib" Repurposed as Inhibitor of Transforming Growth Factor Beta 1 for the Development of Therapeutics for Oral Submucous Fibrosis

982 | Sep 10 2021

Nezar Boreak et al. suggested that the molecule could be validated and implemented for the treatment of OSMF. [Read the Full Post]

An Iron Shield to Protect Epigallocatehin-3-Gallate from Degradation: Multifunctional Self-Assembled Iron Oxide Nanocarrier Enhances Protein Kinase CK2 Intracellular Targeting and Inhibition

785 | Sep 10 2021

Luca Fasolato et al. found that the nanohybrid was able to successfully deliver EGCG into cancer cells, displaying impressive protein kinase CK2 inhibition comparable to that obtained with the most specific CK2 inhibitor, CX-4945 (5.5 vs. 3 µM). [Read the Full Post]

Effect of Dickkopf-1 (Dkk-1) and SP600125, a JNK Inhibitor, on Wnt Signaling in Canine Prostate Cancer Growth and Bone Metastases Wachiraphan Supsavhad 1 2, Bardes B Hassan 1 3,

1510 | Sep 05 2021

Wachiraphan Supsavhad et al. showed that SP600125 had the potential to serve as an alternative adjuvant therapy in some early-stage PCa patients, especially those with high Dkk-1 expression. [Read the Full Post]

G-quadruplex DNA: a novel target for drug design

448 | Sep 03 2021

Fang-Yuan Teng et al. summarized the G4 unfolding mechanisms emerged recently by multiple G4-specific DNA helicases, such as Pif1, RecQ family helicases, FANCJ, and DHX36. [Read the Full Post]

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

0 | Aug 29 2021

Christine Song et al.found an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment. [Read the Full Post]

Pharmacovigilance analysis of cardiac toxicities associated with targeted therapies for metastatic non-small cell lung carcinoma

915 | Aug 25 2021

Sarah Waliany et al. thought that monitoring for heart failure and arrhythmias should be considered with NSCLC targeted therapies, especially osimertinib. [Read the Full Post]

ARTEMIN Promotes Oncogenicity and Resistance to 5-Fluorouracil in Colorectal Carcinoma by p44/42 MAPK Dependent Expression of CDH2

872 | Aug 25 2021

Qiu-Shi Zhuang et al. thought that ARTN might be of prognostic and theranostic utility in CRC. [Read the Full Post]

Clinical benefit of systemic therapies for recurrent ovarian cancer-ESMO-MCBS scores

279 | Aug 20 2021

K E Broekman et al. found that only a few licensed systemic therapies for recurrent ovarian cancer showed substantial clinical benefit based on ESMO-MCBS scores. [Read the Full Post]

Calcyphosine promotes the proliferation of glioma cells and serves as a potential therapeutic target

458 | Aug 15 2021

Zheng Zhu et al. suggested that CAPS promoted the proliferation of glioma by regulating cell cycle and PLK1 inhibitor volasertib might be a chemosensitizer of glioma. [Read the Full Post]

Thermal proteome profiling identifies PIP4K2A and ZADH2 as off-targets of Polo-like kinase 1 inhibitor volasertib

437 | Aug 15 2021

Oksana Goroshchuk et al. suggested that PIP4K2A was a true off-target of volasertib. [Read the Full Post]

Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome

321 | Aug 04 2021

Cheng Zhang et al. thought that CDK4/6 inhibitors including abemaciclib, ribociclib and palbociclib as potential therapeutic targets and might help for therapeutic decision making. [Read the Full Post]

Phase 1 study combining alisertib with nab-paclitaxel in patients with advanced solid malignancies

702 | Jul 23 2021

Kian-Huat Lim et al. thought that the combination of alisertib and nab-paclitaxel had manageable side-effect profile and showed promising preliminary efficacy in high-grade NETs, warranting further testing. [Read the Full Post]

Alpelisib and radiotherapy treatment enhances Alisertib-mediated cervical cancer tumor killing

662 | Jul 23 2021

Yaman Tayyar et al. found that both RT and Alpelisib significantly improved Alisertib-mediated tumor killing. [Read the Full Post]

Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats

2716 | Jul 20 2021

Changju Hou et al. demonstrated that 11R‑VIVIT promoted fracture healing in osteoporotic rats and enhanced the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway. [Read the Full Post]

The mechanisms involved in the resistance of estrogen receptor-positive breast cancer cells to palbociclib are multiple and change over time

462 | Jul 19 2021

Mayu Ono et al. found that ER-positive breast cancer cells used multiple molecular mechanisms to survive in the presence of palbociclib. [Read the Full Post]

Targeting Pyruvate Kinase M2 phosphorylation reverses aggressive cancer phenotypes

592 | Jul 19 2021

Maria Apostolidi et al. found that combinations of Dinaciclib with TEPP-46 reduced cell invasion, impaired redox balance, and triggered cancer cell death. [Read the Full Post]

Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer

262 | Jun 28 2021

Anna Gustafsson et al. thought that the PDS technique was an up-scalable patient-derived drug-testing platform available for gene expression profiling and downstream functional assays. [Read the Full Post]

Allosteric Activation of SARS-CoV-2 RNA-Dependent RNA Polymerase by Remdesivir Triphosphate and Other Phosphorylated Nucleotides

592 | Jun 23 2021

Bing Wang et al. demonstrated that RdRp was allosterically activated by nontemplating phosphorylated nucleotides, including naturally occurring alarmone ppGpp and synthetic remdesivir triphosphate. [Read the Full Post]

A Rho Kinase (ROCK) Inhibitor, Y-27632, Inhibits the Dissociation-Induced Cell Death of Salivary Gland Stem Cells

919 | Jun 23 2021

Kichul Kim et al. demonstrated the protective effects of Y-27632 against dissociation-induced apoptosis of SGSCs during their culture in vitro. [Read the Full Post]

The KRAS G12C Inhibitor MRTX849 Reconditions the Tumor Immune Microenvironment and Sensitizes Tumors to Checkpoint Inhibitor Therapy

685 | Jun 22 2021

David M Briere et al. demonstrated KRAS inhibition reversed an immunosuppressive tumor microenvironment and sensitized tumors to CIT through multiple mechanisms. [Read the Full Post]

Ivacaftor-elexacaftor-tezacaftor and tacrolimus combination in cystic fibrosis

604 | Jun 21 2021

Megan Smith et al. described a pediatric liver transplant recipient with clinical decline related to cystic fibrosis who improved substantially with ETI, without significant impact on the systemic exposure of either ETI or tacrolimus. [Read the Full Post]

Flurbiprofen as a biphenyl scaffold for the design of small molecules binding to PD-L1 protein dimer

840 | Jun 20 2021

Christian Bailly et al. found that the longer FLB derivative HCT1026 appeard as a suitable binder of the PD-L1 dimer, sliding well along the BMS binding cavity. [Read the Full Post]

Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations

239 | Jun 17 2021

Pascal Brouillard et al. demonstrated efficacy of Sirolimus and Alpelisib in treating patients with an LM or PROS. [Read the Full Post]

Modeling clinical responses to targeted therapies by patient-derived organoids of advanced lung adenocarcinoma

609 | Jun 06 2021

Seok-Young Kim et al. demonstrated translational relevance of PDOs in advanced lung adenocarcinoma. [Read the Full Post]

TIP30 overcomes gefitinib resistance by regulating cytoplasmic and nuclear EGFR signaling in non-small cell lung cancer

569 | Jun 01 2021

Shuai Shuai et al. revealed that TIP30 overexpression restored gefitinib sensitivity in NSCLC cells and attenuated the cytoplasmic and nuclear EGFR signaling pathways. [Read the Full Post]

Efficacy and safety of 177 Lu-DOTATATE in lung neuroendocrine tumors: a bi-center study

736 | May 31 2021

Lamiaa Zidan et al. found that in patients with advanced progressive lung NET and satisfactory SSR expression, 177Lu-DOTATATE was effective and safe with a high disease control rate and encouraging PFS and OS. [Read the Full Post]

Efficacy and Safety of Combination Treatment With Apatinib and Osimertinib After Osimertinib Resistance in Epidermal Growth Factor Receptor-Mutant Non-small Cell Lung Carcinoma-A Retrospective Analysis of a Multicenter Clinical Study

481 | May 26 2021

Xue Yang et al. found that the combination of apatinib and osimertinib improved the ORR and the DCR of patients with osimertinib-refractory EGFR-positive NSCLC, thus making it a reasonable treatment choice after the development of osimertinib resistance. [Read the Full Post]

Treatment of liver cancer cells with ethyl acetate extract of Crithmum maritimum permits reducing sorafenib dose and toxicity maintaining its efficacy

243 | May 21 2021

Davide Gnocchi et al. found that combined treatment with C. maritimum ethyl acetate extract and half IC50 sorafenib dose decreased cell proliferation comparably to full-dose sorafenib without increasing cell toxicity as confirmed by the effect on cell cycle regulation and apoptosis. [Read the Full Post]

Thyroglobulin as a negative marker for malignancy in canine and human breast tumors

767 | May 19 2021

Sung-Hyun Hwang et al. found that Tg could be a negative indicator of malignancy in canine and human breast neoplasia. [Read the Full Post]

KRAS secondary mutations that confer acquired resistance to KRAS G12C inhibitors, sotorasib and adagrasib, and overcoming strategies: insights from the in vitro experiments

282 | May 16 2021

Takamasa Koga et al. thought that switching to BI-3406 plus trametinib might be a useful strategy to overcome acquired resistance due to the secondary Y96D/S mutation. [Read the Full Post]

Multiple myeloma: Combination therapy of BET proteolysis targeting chimeric molecule with CDK9 inhibitor

279 | May 07 2021

Su-Lin Lim et al. found that the combination of a BET PROTAC (ARV 825) plus AZD 4573 (CDK9 inhibitor) was effective against MM cells. [Read the Full Post]

CDK9 inhibition improves diabetic nephropathy by reducing inflammation in the kidneys

221 | Apr 26 2021

Xiaojing Yang et al. suggested that CDK9 might serve as a potential therapeutic target for DN. [Read the Full Post]

Synthesis and Evaluation of Biphenyl-1,2,3-Triazol-Benzonitrile Derivatives as PD-1/PD-L1 Inhibitors

596 | Apr 23 2021

Suresh Narva et al. thought that compound 7 was thus a promising candidate for further optimization as an inhibitor of the PD-1/PD-L1 signaling pathway. [Read the Full Post]

In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19

637 | Apr 22 2021

Carolina Q Sacramento et al. found that daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, might be further fostered as an anti-COVID-19 therapy. [Read the Full Post]

Naturally Occurring Resistance Associated Substitutions in Non-Cirrhotic, Treatment Naive HCV-HIV Co-Infected Patients Does Not Affect the Treatment Response for Anti-HCV Antiviral Therapy

628 | Apr 22 2021

Ekta Gupta et al. showed that BL-RAS were common in HCV-HIV co-infected patients. [Read the Full Post]

Therapeutic targeting PLK1 by ON-01910.Na is effective in local treatment of retinoblastoma

708 | Apr 21 2021

Huan Ma et al. demonstrated targetability of PLK1 in retinoblastoma by efficiently causing cell cycle arrest and apoptosis. [Read the Full Post]

A Contaminant Impurity, Not Rigosertib, Is a Tubulin Binding Agent

741 | Apr 21 2021

Stacey J Baker et al. found that these cells failed to proliferate in the presence of rigosertib at concentrations that are lethal to wild-type cells. [Read the Full Post]

The molecular context of vulnerability for CDK9 suppression in triple wild-type melanoma

373 | Apr 19 2021

Samantha M Guhan et al. found that transcriptional blockade through selective targeting of CDK9 was an effective method of suppressing therapeutically-orphaned BRAF/NRAS/NF1 wild-type melanomas. [Read the Full Post]

Water Mapping and Scoring approaches to predict the role of Hydration sites in Binding Affinity of PAK1 inhibitors

443 | Apr 18 2021

Jayashree Biswal et al. determined the best scoring function, established SARs and predicted active molecules through a computational model. [Read the Full Post]

Netarsudil: A new ophthalmic drug in the treatment of chronic primary open angle glaucoma and ocular hypertension

785 | Apr 18 2021

Mansi Batra et al. showed that the discovery of netarsudil was a breakthrough in the therapy of glaucoma with proven efficacy in a wide range of eye pressures and was well tolerated in cases with ocular hypertension and chronic glaucoma. [Read the Full Post]

The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells

1142 | Apr 16 2021

Jing Zhang et al. found that Bcl-2 and Bcl-xL negatively modulated MYC-VX-680 synthetic lethality. [Read the Full Post]

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

1548 | Apr 15 2021

Christine Song et al. suggested an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment. [Read the Full Post]

Melanin Distribution in Human Skin: Influence of Cytoskeletal, Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

1147 | Apr 06 2021

Irene Castellano-Pellicena et al. explored the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. [Read the Full Post]

Protective effects of NAC and salubrinal on apoptosis of retinal pigment epithelial cells induced by all-trans retinoic acid

1095 | Apr 02 2021

Juan Wu et al. thought that ATRA might play an important role in the prevention, diagnosis and treatment of age-related macular degeneration. [Read the Full Post]

Nucleotide variation in histone H2BL drives crossalk of histone modification and promotes tumour cell proliferation by upregulating c-Myc

471 | Mar 30 2021

Lei Zhang et al. revealed that an H2BK5ac-H2BK120ubi crosstalk which regulates gene transcription. [Read the Full Post]

A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells

362 | Mar 28 2021

Chiara Ghezzi et al. thought that CDK7 was a key regulator of glucose consumption in cells with an activated PI3K pathway. [Read the Full Post]

The role of drug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP) and OATP1A/1B and of CYP3A4 in the pharmacokinetics of the CDK inhibitor milciclib

292 | Mar 26 2021

Alejandra Martínez-Chávez found that the low impact of OATP1 and CYP3A could be clinically favorable for milciclib, reducing the risks of unintended drug-drug interactions or interindividual variation in CYP3A4 activity. [Read the Full Post]

CEP131 Abrogates CHK1 Inhibitor-Induced Replication Defects and Is Associated with Unfavorable Outcome in Neuroblastoma

279 | Mar 25 2021

Kiyohiro Ando et al. revealed that MDM2 was associated with CEP131 protein degradation, whereas overexpression of CEP131 accelerated neuroblastoma cell growth and exhibited resistance to CHK1i-induced replication defects. [Read the Full Post]

Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors

494 | Mar 12 2021

Sailu Sarvagalla et al. found that a possible means to develop sub-type selective inhibitor was by targeting Aurora A specific residues (Leu215, Thr217 and Arg220) or Aurora B specific residues (Arg159, Glu161 and Lys164), near the solvent exposed region of the protein. [Read the Full Post]

A screening-based approach identifies cell cycle regulators AURKA, CHK1 and PLK1 as targetable regulators of chondrosarcoma cell survival

432 | Mar 11 2021

Yvonne de Jong et al. thought that AURKA, CHK1 and PLK1 were identified as important survival genes in chondrosarcoma cell lines. [Read the Full Post]

Mnk inhibitors: a patent review

1367 | Mar 07 2021

Ahmed M Abdelaziz et al. provided a succinct review of the current state of development of pyridone-aminal-derived Mnk inhibitors through the analysis of relevant patent applications filed in the last 5 years. [Read the Full Post]

Kinesin-7 CENP-E regulates the formation and structural maintenance of the acrosome

541 | Mar 06 2021

Zhen-Yu She et al. found that light on the molecular mechanisms involved in vesicle trafficking and architecture maintenance of the acrosome. [Read the Full Post]

Comparison of Treatment Effect and Tolerance of the Topical Application of Mizoribine and Cyclosporine A in a Mouse Dry Eye Model

744 | Mar 05 2021

Xiang Lin et al. found that MZR (0.05% in PBS) could be a good competitive product for Restasis because of the comparable treatment effect in dry eye diseases and better ocular tolerability in ocular itch and pain. [Read the Full Post]

PLK1 inhibition sensitizes breast cancer cells to radiation via suppressing autophagy

350 | Mar 04 2021

Baiyao Wang et al. indicated that PLK1 inhibition enhanced the radiosensitivity of breast cancer cells in a manner associated with the suppression of radiation-induced autophagy. [Read the Full Post]

Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae

805 | Feb 25 2021

Christopher A Rice et al. demonstrated the utility of phenotypic screens for discovery of new drugs for pathogenic free-living amoebae, including Acanthamoeba for the first time. [Read the Full Post]

Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer's disease

669 | Feb 24 2021

Mauricio M Oliveira et al. found that attenuating the ISR downstream of phosphorylated eIF2α might restore hippocampal protein synthesis and delay cognitive decline in AD patients. [Read the Full Post]

Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors

742 | Feb 24 2021

Ana J Rodrigues Moita et al. found that priming with HDACi sensitized ovarian cancer cells to treatment with HSP90i or cisplatin and had an influence on the development of cisplatin resistance, both of which might contribute to an improved ovarian cancer treatment. [Read the Full Post]

Multi-functionalised graphene nanoflakes as tumour-targeting theranostic drug-delivery vehicles

554 | Feb 16 2021

Jennifer Lamb et al. showed that GNFs were suitable candidates for use in theranostic drug design. [Read the Full Post]

enAsCas12a Enables CRISPR-Directed Evolution to Screen for Functional Drug Resistance Mutations in Sequences Inaccessible to SpCas9

480 | Feb 14 2021

Jasper Edgar Neggers et al. demonstrated that enAsCas12a is a promising new addition to the CRISPR screening toolbox and allows targeting sites not readily accessible to SpCas9. [Read the Full Post]

Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer

580 | Feb 03 2021

Chih-Yang Wang et al. found that upregulation of PPARA and lipid metabolism-related genes were potential pathways in the carcinogenesis and development of ampullary cancer. [Read the Full Post]

17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma

690 | Feb 03 2021

Shivendra Singh et al. indicated that targeting KDM in combination with chemotherapy might serve as a therapeutic approach to PAX3-FOXO1-positive aRMS. [Read the Full Post]

CKAP2L promotes non-small cell lung cancer progression through regulation of transcription elongation

567 | Jan 28 2021

Tiziana Monteverde et al. found that the molecular mechanisms through which CKAP2L, a protein involved in CIN, promoted cancer progression and suggested that its inhibition represented a novel therapeutic strategy in NSCLC. [Read the Full Post]

Identification of hub genes and small molecule therapeutic drugs related to breast cancer with comprehensive bioinformatics analysis

554 | Jan 28 2021

Mingqian Hao et al. identified six hub genes and 29 potential drug candidates for breast cancer. [Read the Full Post]

De novo protein synthesis is necessary for priming in preclinical models of migraine

944 | Jan 26 2021

Jacob Lackovic et al. suggested that targeting the regulation of protein synthesis might be a novel approach for new migraine treatment strategies. [Read the Full Post]

Kinase activity-independent role of EphA2 in the regulation of M-phase progression

431 | Jan 04 2021

Yuichiro Kaibori et al. suggested that EphA2 regulated M-phase progression in a manner independent of its kinase activity. [Read the Full Post]

Deciphering the Inhibition Mechanism of under Trial Hsp90 Inhibitors and Their Analogues: A Comparative Molecular Dynamics Simulation

591 | Dec 28 2020

Asma Nazar et al. suggested that under trial Hsp90 inhibitors MPC-3100 could be a potential starting point into the development of potential anticancer agents with the possibility of future directions for the improvement of early existing Hsp90 inhibitors CNF-2024 and SNX-5422 as an anticancer agent. [Read the Full Post]

Heat Shock Protein 90 Inhibitors AUY922, BIIB021 and SNX5422 Induce Bim-mediated Death of Thyroid Carcinoma Cells

622 | Dec 27 2020

Si Hyoung Kim et al. found that AUY922, BIIB021 and SNX5422 induced cytotoxicity by modulating Bim and ERK1/2, AKT and AMPK signaling in thyroid carcinoma cells. [Read the Full Post]

The phosphorylation of CHK1 at Ser345 regulates the phenotypic switching of vascular smooth muscle cells both in vitro and in vivo

397 | Dec 25 2020

Chen Xin et al. demonstrated that phosphorylation of CHK1 under DNA damage stress modulated VSMCs phenotypic switching. [Read the Full Post]

Y-27632 Induces Neurite Outgrowth by Activating the NOX1-Mediated AKT and PAK1 Phosphorylation Cascades in PC12 Cells

278 | Dec 25 2020

So Yeong Park et al. suggested that Rac1/NOX1-dependent ROS generation and subsequent activation of the AKT/PAK1 cascade contributed to Y-27632-induced neurite outgrowth in PC12 cells. [Read the Full Post]

Crystal Structure of the Kinase Domain of MerTK in Complex with AZD7762 Provides Clues for Structure-Based Drug Development

272 | Dec 23 2020

Tae Hyun Park et al. determined the crystal structure of the MerTK:AZD7762 complex and revealed the binding mode of AZD7762 to MerTK. [Read the Full Post]

FTY720 induces ferroptosis and autophagy via PP2A/AMPK pathway in multiple myeloma cells

625 | Dec 20 2020

Yuan Zhong et al. provided a new perspective on the treatment of MM. [Read the Full Post]

HSP90 Inhibitor Ganetespib (STA-9090) Inhibits Tumor Growth in c-Myc-Dependent Esophageal Squamous Cell Carcinoma

685 | Dec 17 2020

Liuliu Guan et al. supported that the HSP90 inhibitor, STA-9090, suppressed the expression of the MYC protein and interferes with HSP90-MYC protein-protein interaction. [Read the Full Post]

Ganetespib in Combination with Pemetrexed-Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial

780 | Dec 16 2020

Dean A Fennell et al. found that ganetespib could be combined safely with pemetrexed and platinum chemotherapy to treat patients with MPM. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

1558 | Dec 13 2020

Ryo Kanamoto et al. demonstrated an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis

0 | Dec 12 2020

Alejandro Torres-Hernandez et al. found that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis. [Read the Full Post]

Novel miRNAs as Potential Regulators of PD-1/PD-L1 Immune Checkpoint, and Prognostic Value of MIR9-1 and MIR124-2 Methylation in Ovarian Cancer

527 | Dec 05 2020

N E Kushlinskii et al. suggested the role of inhibitors of the sPD-L1 immune checkpoint for five miRNAs (miR-124, miR-34b, miR-34c, miR-9, miR-339) and the possibility of using hypermethylated MIR9-1. [Read the Full Post]

LGR5 induces β activation and augments tumor progression by activating STAT3 in human intrahepatic cholangiocarcinoma

1062 | Dec 04 2020

Keishi Kawasaki et al. thought that LGR5 was an excellent prognostic predictor and a promising therapeutic target for ICC. [Read the Full Post]

FXIIIa substrate peptide decorated BLZ945 nanoparticles for specifically remodeling tumor immunity

538 | Nov 30 2020

Qi Wei et al. established a novel combination strategy for anti-tumor therapy. [Read the Full Post]

Design and Evaluation of Rhein-Based MRI Contrast Agents for Visualization of Tumor Necrosis Induced by Combretastatin A-4 Disodium Phosphate

463 | Nov 30 2020

Libang Zhang et al. found that GdP1 might serve as a potential candidate for early evaluation of tumor response to CA4P treatment. [Read the Full Post]

Resistance to the CHK1 inhibitor prexasertib involves functionally distinct CHK1 activities in BRCA wild-type ovarian cancer

283 | Nov 29 2020

Jayakumar Nair et al. demonstrated new mechanistic insights of functionally distinct CHK1 activities and highlighted a potential combination treatment approach to overcome CHK1i resistance in BRCAwt HGSOC. [Read the Full Post]

Bevacizumab plus fosbretabulin in recurrent ovarian cancer: Overall survival and exploratory analyses of a randomized phase II NRG oncology/gynecologic oncology group study

430 | Nov 29 2020

Krishnansu S Tewari et al. found that although no significant survival benefit was observed, the trend showing a reduced HR for progression or death with increasing tumor size when fosbretabulin was added to bevacizumab compared to bevacizumab alone warrants further study. [Read the Full Post]

Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines

262 | Nov 27 2020

Carmelina Antonella Iannuzzi et al. suggested that the dl922-947-AZD1775 combination could be a feasible strategy against MM. [Read the Full Post]

An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

768 | Nov 22 2020

Sunita Shankar et al. supported a biphasic model of pancreatic cancer development: an AGO2-independent early phase of PanIN formation reliant on EGFR-RAS signaling, and an AGO2-dependent phase wherein the mutant KRAS-AGO2 interaction was critical for PDAC progression. [Read the Full Post]

RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice

644 | Nov 18 2020

Jingxian Chen et al. showed that RIP3 participated in the NLRP3 inflammasome activation in infiltrating macrophages in ALI induced by LPS. [Read the Full Post]

Identification of Quinazolinone Analogs Targeting CDK5 Kinase Activity and Glioblastoma Cell Proliferation

251 | Nov 12 2020

Marion Peyressatre et al. found that the quinazolinone derivatives were the first small molecules reported to target CDK5 at a site other than the ATP pocket, thereby constituting attractive leads for glioblastoma therapeutics and providing therapeutic perspectives for neurodegenerative diseases. [Read the Full Post]

Ginsenoside Rg1 reduces β‑amyloid levels by inhibiting CDΚ5‑induced PPARγ phosphorylation in a neuron model of Alzheimer's disease

576 | Nov 12 2020

Qiankun Quan et al. suggested that ginsenoside Rg1 had neuroprotective properties and had potential for use in the treatment of AD. [Read the Full Post]

Optimization and Evaluation of Propolis liposomes as a promising therapeutic approach for COVID-19

558 | Nov 11 2020

Hesham Refaat et al. identified the potential of propolis liposomes as a promising treatment approach against COVID-19. [Read the Full Post]

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel-resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe

226 | Nov 09 2020

Stanislav Drápela et al. suggested that metabolically robust and selective CHK1 inhibitor MU380 could bypass docetaxel resistance and improve the effectiveness of GEM in DR mCRPC models. [Read the Full Post]

Phosphoproteomics Analysis Reveals a Potential Role of CHK1 in Regulation of Innate Immunity through IRF3

281 | Nov 09 2020

Zhen Chen et al. indicated that the CHK1-dependent regulation of IRF3 phosphorylation at S173 and S175 might play a role in the induction of innate immune response after replication stress or DNA damage, which suggested a potential function of CHK1 in the innate immune response. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

0 | Nov 06 2020

Poojabahen Tajpara et al. discovered that both drugs had a comparable efficacy for inhibiting HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir-resistant strains. [Read the Full Post]

Identification of antiviral compounds against equid herpesvirus-1 using real-time cell assay screening: Efficacy of decitabine and valganciclovir alone or in combination

269 | Nov 05 2020

Côme Thieulent et al. showed that deoxycytidine reverts the antiviral effect of decitabine, thus supporting some competition at the level of nucleoside phosphorylation by deoxycytidine kinase and/or DNA synthesis. [Read the Full Post]

VDAC upregulation and αTAT1‑mediated α‑tubulin acetylation contribute to tanespimycin‑induced apoptosis in Calu‑1 cells

2111 | Nov 02 2020

Qilin Wang et al. provided evidence for the use of a combination of drugs that target VDAC1 and tubulin to induce tumour cell apoptosis. [Read the Full Post]

Identification of Subtype-Specific Metastasis-Related Genetic Signatures in Sarcoma

785 | Nov 02 2020

Ya-Ling Li et al. provided new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provided new directions for further study of sarcoma. [Read the Full Post]

Small molecule 2,3-DCPE induces S phase arrest by activating the ATM/ATR-Chk1-Cdc25A signaling pathway in DLD-1 colon cancer cells

674 | Oct 29 2020

Bingjun Bai et al. suggested that 2,3-DCPE caused DNA damage in colon cancer cells and that 2,3-DCPE-induced S phase arrest was associated with the activation of the ATM/ATR-Chk1-Cdc25A pathway. [Read the Full Post]

Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

838 | Oct 27 2020

E M Samoilova et al. found that reprogramming with small molecules without additional factors modifying gene expression did not allow reproducible production of human neural stem cell-like progenitors that could be used as the source of neural tissue for the regenerative therapy. [Read the Full Post]

Hsp90 Inhibitor; NVP-AUY922 in Combination with Doxorubicin Induces Apoptosis and Downregulates VEGF in MCF-7 Breast Cancer Cell Line

812 | Oct 16 2020

Mahshid Mohammadian et al. indicated an effective action of NVP-AUY922 in combined with DOX in this cell line. [Read the Full Post]

Radiosensitization by Kinase Inhibition Revealed by Phosphoproteomic Analysis of Pancreatic Cancer Cells

454 | Oct 16 2020

Svenja Wiechmann et al.improved the understanding of radioresistance and provided avenues for developing radiotherapeutic strategies. [Read the Full Post]

Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy

852 | Oct 15 2020

Ankit K Rochani et al.suggested that DNP-based aqueous nanoformulations could be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy. [Read the Full Post]

An exon skipping screen identifies antitumor drugs that are potent modulators of pre-mRNA splicing, suggesting new therapeutic applications

686 | Oct 14 2020

Yihui Shi et al.supported the broad potential for the development of agents that targeted the spliceosome for the treatment of cancer and other diseases, as well as new avenues for the discovery of new chemotherapeutic agents for a range of diseases. [Read the Full Post]

A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients

676 | Sep 29 2020

Li Ding et al. suggested that cotransplantation of HLA-haploidentical HSC and allogenic mesenchymal stem cell might provide an effective and safe treatment for children and adolescents with SAA who lacked matched donors. [Read the Full Post]

CTELS: A Cell-Free System for the Analysis of Translation Termination Rate

669 | Sep 28 2020

Kseniya A Lashkevich et al. revealed a transient stalling event at a "leaky" stop codon context, which likely defined the basis of nonsense suppression. [Read the Full Post]

Phase Ib Study of Ribociclib Plus Fulvestrant and Ribociclib Plus Fulvestrant Plus PI3K-Inhibitor (Alpelisib or Buparlisib) for HR+ Advanced Breast Cancer

258 | Sep 23 2020

Sara M Tolaney et al .showed that Ribociclib plus fulvestrant demonstrated safety in the treatment of patients with HR+, HER2- ABC. [Read the Full Post]

Inhibition of Aurora Kinase B attenuates fibroblast activation and pulmonary fibrosis

364 | Sep 21 2020

Rajesh K Kasam et al. provided important proof-of-concept that demonstrated barasertib as a possible intervention therapy for IPF. [Read the Full Post]

Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets

469 | Sep 21 2020

Julia Krushkal et al. indicated potential epigenetic mechanisms affecting SCLC response to chemotherapy and suggested targets for combination therapies. [Read the Full Post]

Protein Kinase CK2 in Cancer Energetics

959 | Aug 27 2020

Eduardo Silva-Pavez et al. proposed that the specific inhibition of CK2 might lead to a catastrophic death of cancer cells, which could become a feasible therapeutic strategy to beat this devastating disease. [Read the Full Post]

Casein kinase 2 inhibitor CX-4945 elicits an anti-Warburg effects through the downregulation of TAp73 and inhibits gastric tumorigenesis

856 | Aug 27 2020

Shengli Tang et al. suggested that CX-4945 elicited an anti-Warburg effects in gastric cancer overexpressing Tap73 and inhibited gastric tumorigenesis. [Read the Full Post]

GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration

1318 | Aug 19 2020

Youpei Wang et al. provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration. [Read the Full Post]

The rRNA synthesis inhibitor CX-5461 may induce autophagy that inhibits anticancer drug-induced cell damage to leukemia cells

388 | Aug 18 2020

Shuichiro Okamoto et al. showed the autophagy which might be induced by CX-5461 was the second type. [Read the Full Post]

Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes

726 | Aug 10 2020

Adrien Foca et al. emphasized that a specific PLK1 inhibition could help in achieving an improved HBsAg loss in CHB patients, likely in combination with other HBsAg-targeting strategies. [Read the Full Post]

Gemcitabine combined with cisplatin vs. taxane, cisplatin, and fluorouracil in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective case-control study

673 | Aug 04 2020

Y-M Huang et al. showed that the clinical efficacy of the GP regimen combined with CCRT for the treatment of locoregionally advanced NPC might be better than that of the TPF regimen. [Read the Full Post]

The Apparent Requirement for Protein Synthesis during G2 Phase Is due to Checkpoint Activation

338 | Jul 29 2020

Sarah Lockhead et al. showed that protein synthesis during G2 phase was not required for mitotic entry, at least when the p38 checkpoint pathway was abrogated. [Read the Full Post]

Polo-like kinase 1 as a promising diagnostic biomarker and potential therapeutic target for hepatocellular carcinoma

446 | Jul 22 2020

Eman H Yousef et al. found that Polo-like kinase 1 might be a potential biomarker for hepatocellular carcinoma diagnosis and follow-up during treatment with chemotherapies. [Read the Full Post]

DrugSniper, a Tool to Exploit Loss-Of-Function Screens, Identifies CREBBP as a Predictive Biomarker of VOLASERTIB in Small Cell Lung Carcinoma (SCLC)

365 | Jul 21 2020

Fernando Carazo et al. showed the potential of genome-wide loss-of-function screens to identify new personalized therapeutic hypotheses in SCLC and potentially in other tumors, which was a valuable starting point for further drug development and drug repositioning projects. [Read the Full Post]

Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial

701 | Jul 17 2020

Andrew M Brunner et al. suggested that alisertib combined with induction chemotherapy is active and safe in previously untreated patients with high-risk acute myeloid leukaemia. [Read the Full Post]

Cyclin-Dependent Kinase 4/6 Inhibitors Combined With Radiotherapy for Patients With Metastatic Breast Cancer

282 | Jul 08 2020

Ivica Ratosa et al. observed a modest increase in the rates of grade 3 or higher AEs after combined RT and CDK4/6i, with maintained efficacy of concomitant RT. [Read the Full Post]

Effects of the PI3K/Akt Signaling Pathway on the Apoptosis of Early Host Cells Infected With Eimeria Tenella

1305 | Jun 21 2020

Xuesong Zhang et al. investigated the role of PI3K/Akt signaling pathway on host cell apoptosis in the early infection of Eimeria tenella,the early development of E. tenella could inhibit host cell apoptosis by downregulating the Caspase-3 activity. [Read the Full Post]

Inhibition of Aurora Kinase A by Alisertib Reduces Cell Proliferation and Induces Apoptosis and Autophagy in HuH-6 Human Hepatoblastoma Cells

549 | Jun 19 2020

Jingyi Tan et al. suggested that AURKA may be a novel therapeutic target and ALS a potential therapeutic drug for the treatment of HB. [Read the Full Post]

Prediction of Therapeutic Outcome and Survival in a Transgenic Mouse Model of Pancreatic Ductal Adenocarcinoma Treated With Dendritic Cell Vaccination or CDK Inhibitor Using MRI Texture: A Feasibility Study

475 | Jun 17 2020

Aydin Eresen et al. demonstrated that MRI texture features had great potential to generate diagnosis and prognosis models for monitoring early treatment response following dinaciclib drug or DC vaccine treatment and also predicting histopathological tumor markers and long-term clinical outcomes. [Read the Full Post]

Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2

525 | Jun 16 2020

Erik B Faber et al. detailed the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increased the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. [Read the Full Post]

Palbociclib (PD0332991)-a Selective and Potent Cyclin-Dependent Kinase Inhibitor: A Review of Pharmacodynamics and Clinical Development

0 | May 21 2020

Amy S Clark et al. found that Palbociclib was well tolerated and had therapeutic potential for multiple cancers, including breast cancer, where its efficacy had been demonstrated alone and in combination with endocrine therapy. [Read the Full Post]

Inhibition of Rb phosphorylation leads to H2S-mediated inhibition of NF-kB in acute pancreatitis and associated lung injury in mice

290 | May 17 2020

Sundar V et al. revealed a novel link between H2S/RB/NF-κB pathways, in AP and provided insight into possible mechanism that can be targeted in prevention of inflammation to cancer development. [Read the Full Post]

Glucagon-like peptide 1 reverses myocardial hypertrophy through cAMP/PKA/RhoA/ROCK2 signaling.

1002 | May 14 2020

Fan S et al. suggested that GLP-1 might reverse myocardial hypertrophy through the PKA/RhoA/ROCK2 signaling pathway. [Read the Full Post]

The Rho-associated kinase inhibitor fasudil can replace Y-27632 for use in human pluripotent stem cell research

1361 | May 12 2020

So S et al. suggested that fasudil can replace Y-27632 for use in stem research. [Read the Full Post]

RO-3306 prevents postovulatory aging-mediated spontaneous exit from M-II arrest in rat eggs cultured in vitro

304 | May 04 2020

Prasad S et al. resulted suggest that postovulatory aging destabilizes MPF by modulating specific phosphorylation of Cdk1 and cyclin B1 level. RO-3306 prevented these changes and maintained M-II arrest in rat eggs cultured in vitro. Hence, maintenance of M-II arrest in ovulated eggs using RO-3306 could be beneficial to increase the number of eggs available for various ART programs. [Read the Full Post]

Covalent CDK7 Inhibitor THZ1 Inhibits Myogenic Differentiation

333 | Apr 27 2020

Xinqi Ma et al. indicated that THZ1 inhibits myogenic differentiation, suggesting that therapies based on THZ1 might have potential side effects on muscle functions. [Read the Full Post]

A Phase I Study of PF-04929113 (SNX-5422), an Orally Bioavailable Heat Shock Protein 90 Inhibitor, in Patients With Refractory Solid Tumor Malignancies and Lymphomas

614 | Apr 19 2020

Arun Rajan et al. showed that PF-04929113 administered orally twice a week is well tolerated and inhibits its intended target Hsp90. No objective responses were seen, but long-lasting stabilizations were obtained. Although no clinically significant drug-related ocular toxicity was seen in this study, the development of PF-04929113 has been discontinued because of ocular toxicity seen in animal models and in a separate phase I study. [Read the Full Post]

SNX-2112, a Selective Hsp90 Inhibitor, Potently Inhibits Tumor Cell Growth, Angiogenesis, and Osteoclastogenesis in Multiple Myeloma and Other Hematologic Tumors by Abrogating Signaling via Akt and ERK

572 | Apr 19 2020

Yutaka Okawa et al. provided the framework for clinical studies of SNX-2112 to improve patient outcome in MM and other hematologic malignancies. [Read the Full Post]

Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4

468 | Apr 14 2020

Mills SC et al. suggest that Rac1 activation is not necessary for CCL3 signalling, and reveal that NSC23766 could be a novel CXCR4 receptor ligand. [Read the Full Post]

A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients

340 | Apr 13 2020

Laquente B et al. showed that LY2603618/gemcitabine was not superior to gemcitabine for the treatment of patients with pancreatic cancer. [Read the Full Post]

Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling

378 | Apr 12 2020

Wang L et al. indicated that in addition to acting as a tumor suppressor, AZD7762 may prevent bone loss by inhibiting osteoclastogenesis and stimulating osteoblast mineralization. [Read the Full Post]

Development Of Novel Liposome-Encapsulated Combretastatin A4 Acylated Derivatives: Prodrug Approach For Improving Antitumor Efficacy

532 | Apr 08 2020

Gu Y et al. suggested that the release or hydrolysis of the parent drug from the prodrug was closely related with the in vitro and in vivo properties. The slow drug release of CA4 modified with longer acyl chain could prolong the circulation time and increase the concentration of the drug in the tumor tissue. These effects play a critical role in increasing the antitumor efficacy. [Read the Full Post]

Covalent functionalization of SWCNT with combretastatin A4 for cancer therapy

533 | Apr 08 2020

Assali M et al. suggested that the novel SWCNT-CA4 has a significant anticancer activity that might be superior to that of free CA4. [Read the Full Post]

Prexasertib treatment induces homologous recombination deficiency and synergizes with olaparib in triple-negative breast cancer cells

303 | Apr 07 2020

Mani C et al. indicted that RAD51 could be a biomarker for aggressive TNBC and for racial disparity in breast cancer. As positive correlation exists between RAD51 and CHEK1 expression in breast cancer, the in vitro preclinical data presented here provides additional mechanistic insights for further evaluation of the rational combination of prexasertib and olaparib for improved outcomes and reduced racial disparity in TNBC. [Read the Full Post]

CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib

421 | Apr 07 2020

Sen T et al. provided a preclinical proof of concept supporting the initiation of a clinical efficacy trial in patients with platinum-sensitive or platinum-resistant relapsed SCLC. [Read the Full Post]

Orthotopic patient-derived xenografts of paediatric solid tumours

394 | Apr 06 2020

Stewart E et al. identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma orthotopic patient-derived xenografts tumours in vivo. [Read the Full Post]

Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer

389 | Mar 31 2020

Molina-Arcas M et al. provided a rationale for the design of combination treatments to enhance the impact of the KRAS-G12C inhibitors, which are now entering clinical trials. [Read the Full Post]

Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD)

744 | Mar 15 2020

Nikonova AS et al. identified a new biologic activity for HSP90 and support a cilia-based mechanism for cyst repression.-Nikonova, A. S., Deneka, A. Y., Kiseleva, A. A., Korobeynikov, V., Gaponova, A., Serebriiskii, I. G., Kopp, M. C., Hensley, H. H., Seeger-Nukpezah, T. N., Somlo, S., Proia, D. A., Golemis, E. A. Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD). [Read the Full Post]

The novel HSP90 inhibitor STA-9090 exhibits activity against Kit-dependent and -independent malignant mast cell tumors

670 | Mar 15 2020

Lin TY et al. showed that STA-9090 exhibits broad activity against mast cells expressing WT or mutant Kit, suggesting it may be an effective agent in the clinical setting against mast cell malignancies. [Read the Full Post]

WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

398 | Mar 14 2020

Zheng H et al. demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. [Read the Full Post]

The Role and Mechanism of CRT0066101 as an Effective Drug for Treatment of Triple-Negative Breast Cancer

840 | Mar 09 2020

Liu Y et al. indicated that PRKD inhibitor CRT0066101 exhibits anti-TNBC effects via modulating a phosphor-signaling network and inhibiting the phosphorylation of many cancer-driving factors, including MYC, MAPK1/3, AKT, YAP, and CDC2, providing insight into the important roles as well as the molecular mechanism of CRT0066101 as an effective drug for TNBC. [Read the Full Post]

Targeting KRAS Mutant Cancers With a Covalent G12C-Specific Inhibitor

450 | Feb 17 2020

Matthew R Janes et al. provided in vivo evidence that mutant KRAS can be selectively targeted and reveals ARS-1620 as representing a new generation of KRASG12C-specific inhibitors with promising therapeutic potential. [Read the Full Post]

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

0 | Feb 13 2020

Wang Y et al. suggested improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention. [Read the Full Post]

Rho-kinase ROCK inhibitors reduce oligomeric tau protein

1099 | Feb 10 2020

Hamano T et al. suggested that ROCK inhibitors represent a viable therapeutic route to reduce the pathogenic forms of tau protein in tauopathies, including Alzheimer's disease. [Read the Full Post]

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive Her2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

327 | Feb 08 2020

Demir A et al. demonstrated that the efficacy of palbociclib among heavily treated hormone receptor-positive/HER2-negative advanced BC patients was acceptable clinical benefit, and it was generally well tolerated among this population. [Read the Full Post]

Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance

360 | Jan 27 2020

Khalil HS et al. argue that optimisation of the therapeutic effects of kinase inhibitors such as Seliciclib could be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division. [Read the Full Post]

Tumor-Directed Therapeutic Targets in Cushing Disease

384 | Jan 27 2020

Theodoropoulou M et al. indicated that for many patients with CD, effective tumor-targeted pharmacological therapy is still lacking. Coordinated efforts are pivotal in establishing efficacy and safety of novel therapeutics in this rare but devastating disease. [Read the Full Post]

Protective effect of roscovitine against rotenone-induced parkinsonism

390 | Jan 26 2020

Chen Y et al. indicated that mouse models of Parkinson's disease were established by oral rotenone administration and reproduced some of the features of dopaminergic neuronal degeneration. Roscovitine protects against rotenone-induced parkinsonism. [Read the Full Post]

Chk1 inhibitor SCH 900776 enhances the antitumor activity of MLN4924 on pancreatic cancer

0 | Jan 22 2020

Li JA et al. provided the preclinical evidence and the rationale of the combination therapy of MLN4924 with SCH 900776 or other Chk1 inhibitors to treat PC. [Read the Full Post]

CDK4/6 Inhibitor Palbociclib Amplifies the Radiosensitivity to Nasopharyngeal Carcinoma Cells via Mediating Apoptosis and Suppressing DNA Damage Repair

330 | Jan 16 2020

Xie X et al. demonstrated that palbociclib could provoke a strong antitumor activity as a potential adjuvant to radiation therapy for NPC harboring RB expression. [Read the Full Post]

MK-8776, a novel chk1 kinase inhibitor, radiosensitizes p53-defective human tumor cells

388 | Jan 15 2020

Bridges KA et al. indicated that MK-8776 radiosensitizes tumor cells by mechanisms that include abrogation of the G2 block and inhibition of DSB repair. Our findings support the clinical evaluation of MK-8776 in combination with radiation. [Read the Full Post]

Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis

427 | Jan 13 2020

Quenelle DC et al. concluded pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, including herpes simplex encephalitis. [Read the Full Post]

Preparation and evaluation of 99mTc-labeled HYNIC-palbociclib analogs for cyclin-dependent kinase 4/6-positive tumor imaging

363 | Jan 11 2020

Gan Q et al. indicated that 99mTc-tricine-TPPTS-L is a promising tumor imaging agent that targets CDK4/6. [Read the Full Post]

17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model

787 | Jan 08 2020

Joshi SS et al. indicated their sdudies support a role for 17-AAG and HSP90 inhibition in enhancing cellular immunotherapy for melanoma. [Read the Full Post]

Tanespimycin as antitumor therapy

0 | Jan 07 2020

Dimopoulos MA et al. indiacated that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

0 | Jan 03 2020

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

Targeting the cell cycle in head and neck cancer by Chk1 inhibition: a novel concept of bimodal cell death

320 | Dec 22 2019

van Harten AM et al. concluded that Chk1 has become a key molecule in HNSCC cell cycle regulation and a very promising therapeutic target. Chk1 inhibition leads to S-phase apoptosis or death in mitosis. We provide a potential efficacy biomarker and combination therapy to follow-up in clinical setting. [Read the Full Post]

Hsp90 inhibitors induce the unfolded protein response in bovine and mice lung cells

722 | Dec 19 2019

Kubra KT et al. demonstrated that Hsp90 inhibition triggers the activities of the unfolded protein response, and suggests that this molecular machinery contributes in the protective action of Hsp90 inhibitors in the lung microvasculature. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

0 | Dec 19 2019

Lian J et al. indicated that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions

729 | Dec 18 2019

Piotrowska Z et al.showed that this study met its primary end point, suggesting that luminespib may be an active therapy for advanced NSCLC patients with EGFR ins20. Luminespib is generally well-tolerated, though reversible low-grade ocular toxicity is common. Further study of luminespib and other hsp90 inhibitors in this population is warranted. [Read the Full Post]

Reactive oxygen species generation and increase in mitochondrial copy number: new insight into the potential mechanism of cytotoxicity induced by aurora kinase inhibitor, AZD1152-HQPA

521 | Dec 13 2019

Zekri A et al. showed a functional relationship between the aurora kinase inhibition, an increase in mitochondrial copy number, and ROS generation in therapeutic modalities of cancer. This study suggests that the excessive ROS generation may be a novel mechanism of cytotoxicity induced by the aurora kinase inhibitor, AZD1152-HQPA. [Read the Full Post]

Fludarabine-PET in a murine model of multiple myeloma

974 | Dec 08 2019

Hovhannisyan N et al. suggested that [18F]fludarabine-PET might represent an alternative and perhaps more specific modality for MM imaging when compared to [18F]FDG. Nevertheless, more investigations are required to extend this conclusion to humans. [Read the Full Post]

Inhibitory Activities of Blasticidin S Derivatives on Aflatoxin Production by Aspergillus Flavus

0 | Dec 06 2019

Yoshinari T et al. indicated that the inhibitory activity of BcS against aflatoxin production was enhanced by esterification of its carboxyl group and that the carboxymethyl ester derivative might be more suitable for practical use than BcS because of the specificity of the carboxymethyl ester derivative, which inhibited aflatoxin production more than BcS. [Read the Full Post]

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

0 | Nov 28 2019

Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]

Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice

537 | Nov 11 2019

Hosseini-Zare MS et al. showed that seizure activities were affected by pentoxifylline, H-89 and bucladesine via interactions with intracellular cAMP and cGMP signaling pathways, cyclic nucleotide-dependent protein kinases, and related neurotransmitters. [Read the Full Post]

CX-4945: the protein kinase CK2 inhibitor and anti-cancer drug shows anti-fungal activity

992 | Nov 07 2019

Masłyk M et al. indicated their data unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may simultaneously prevent cancer-associated candidiasis. [Read the Full Post]

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

0 | Oct 29 2019

Xu H et al. indicated these data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016). [Read the Full Post]

BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1

581 | Oct 19 2019

Gohda J et al. found that BI-2536 synergistically activates the latent provirus in combination with SAHA, a histone deacetylase inhibitor, or the non-tumour-promoting phorbol ester prostratin. Our findings strongly suggest that BI-2536 and BI-6727 are potent LRAs for the "shock and kill" HIV-1 eradication strategy. [Read the Full Post]

The Herb-Drug Pharmacokinetic Interaction of 5-Fluorouracil and Its Metabolite 5-Fluoro-5,6-Dihydrouracil with a Traditional Chinese Medicine in Rats

450 | Oct 17 2019

Liu JH et al. indicated the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice. [Read the Full Post]

Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis

0 | Oct 10 2019

Chen G et al. provided a novel therapeutic strategy to optimize MK-1775 treatment efficiency in lung cancers. [Read the Full Post]

Inhibition of Suicidal Erythrocyte Death by Volasertib

0 | Sep 30 2019

Al Mamun Bhuyan A et al. showed that Volasertib is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion and hyperosmotic shock, effects contrasting the stimulation of K562 cell apoptosis. [Read the Full Post]

BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity

0 | Sep 30 2019

Rudolph D et al. indicated these findings warrant further investigation of BI 6727 as a tailored antimitotic agent; clinical studies have been initiated. [Read the Full Post]

Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine

332 | Sep 18 2019

Gelbert LM et al. identified a potent, orally active small-molecule inhibitor of CDK4/6 that is active in xenograft tumors. LY2835219is currently in clinical development. [Read the Full Post]

NK2 receptor mediated detrusor muscle contraction involves Gq/11-dependent activation of voltage-dependent calcium channels and the RhoA-Rho kinase pathway

1117 | Aug 30 2019

Dér B et al. identified potential therapeutic targets of bladder dysfunctions related to upregulation of TKs. [Read the Full Post]

Functional genomics identifies predictive markers and clinically actionable resistance mechanisms to CDK4/6 inhibition in bladder cancer

382 | Aug 29 2019

Tong Z et al. found that identification of potential predictive markers, resistance mechanisms and rational combination therapies could be achieved by applying a CRISPR-dCas9 screening approach in bladder cancer. [Read the Full Post]

Alisertib demonstrates significant antitumor activity in bevacizumab resistant, patient derived orthotopic models of glioblastoma

570 | Aug 20 2019

Kurokawa C et al. showed that alisertibdisplays significant antitumor activity against primary GBM lines and xenografts, including patient derived GBM lines resistant to bevacizumab; these data support clinical translation in GBM. [Read the Full Post]

Selective BCL-XL inhibition promotes apoptosis in combination with MLN8237 in medulloblastoma and pediatric glioblastoma cells

606 | Aug 20 2019

Levesley J et al. indicated that selective small-molecule inhibitors of BCL-XL may enhance the efficacy of MLN8237 and other targeted chemotherapeutic agents. [Read the Full Post]

Overview of CDK9 as a target in cancer research

460 | Aug 13 2019

Morales F et al. concluded that there are many small molecules that bind to CDK9, but their lack of selectivity against other CDKs do not allow them to get to the clinical use. However, drug designers currently have the tools needed to improve the selectivity of CDK9 inhibitors and to make successful treatment available to patients. [Read the Full Post]

Efficacy of the CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute lymphoblastic leukemia

0 | Aug 12 2019

Moharram SA et al. identified the CDK inhibitor dinaciclib as a potential drug for T-ALL. Dinaciclib treatment significantly reduced cell viability and completely blocked colony formation. Furthermore, cells treated with dinaciclibshowed decreased expression of several pro-survival proteins including survivin, cyclin T1 and c-MYC. Dinaciclib treatment also increased accumulation of cells in G2/M phase and significantly induced apoptosis. Finally, dinaciclib extended survival of mice in a T-ALL cell xenograft model. Collectively, these data suggest that the CDK inhibitor dinaciclib is an active drug for T-ALL in the preclinical settings. [Read the Full Post]

Palbociclib (PD0332991)-a Selective and Potent Cyclin-Dependent Kinase Inhibitor: A Review of Pharmacodynamics and Clinical Development

572 | Jul 17 2019

Clark AS et al. indicated that palbociclib is well tolerated and has therapeutic potential for multiple cancers, including breast cancer, where its efficacy has been demonstrated alone and in combination with endocrine therapy. Additional combinations of palbociclib with endocrine therapy, chemotherapy, and targeted therapy have potential in various tumors, and phase 3 trials are under way. [Read the Full Post]

Airway Progenitor Clone Formation Is Enhanced by Y-27632-Dependent Changes in the Transcriptome

1273 | Jul 10 2019

Reynolds SD et al. concluded that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification. [Read the Full Post]

Characterization of Three Novel H3F3A-mutated Giant Cell Tumor Cell Lines and Targeting of Their Wee1 Pathway

527 | Jul 09 2019

Lübbehüsen C et al, offered valuable new tools for GCTB studies and presents a description of novel biomarkers and molecular targeting strategies. [Read the Full Post]

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

757 | Jun 17 2019

Wang Y et al. suggested improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention. [Read the Full Post]

Effect of CHK1 Inhibition on CPX-351 Cytotoxicity in vitro and ex vivo

415 | Jun 10 2019

Vincelette ND et al. showed that CHK1 inhibition increases the antiproliferative effect of CPX-351 on primary AML specimens ex vivo, offering the possibility that CPX-351 may be well suited to combine with CHK1-targeted agents. [Read the Full Post]

Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour-bearing dogs: A phase I dose finding study

577 | Jun 09 2019

Wouda RM et al. indicated the dose-limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well-tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials. [Read the Full Post]

CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death

957 | Jun 08 2019

Mandato E et al. suggested a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in the DLBCL. [Read the Full Post]

Inhibitory Activities of Blasticidin S Derivatives on Aflatoxin Production by Aspergillus Flavus

527 | Jun 03 2019

Yoshinari T et al. indicated that the inhibitory activity of BcS against aflatoxin production was enhanced by esterification of its carboxyl group and that the carboxymethyl ester derivative might be more suitable for practical use than BcS because of the specificity of the carboxymethyl ester derivative, which inhibited aflatoxin production more than BcS. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

963 | May 31 2019

Lian J et al. showed that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells

1025 | May 31 2019

Diep DTV et al. indicated that KD025suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2. [Read the Full Post]

Chk1 inhibitor SCH 900776 enhances the antitumor activity of MLN4924 on pancreatic cancer

499 | May 28 2019

Li JA et al. provided the preclinical evidence and the rationale of the combination therapy of MLN4924 with SCH 900776 or other Chk1 inhibitors to treat PC. [Read the Full Post]

The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA)

618 | May 27 2019

Zekri A et al. showed for the first time the potential contribution of miRNAs in the anti-cancer effects of AZD1152-HQPA. [Read the Full Post]

Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib

890 | May 26 2019

Vyse S et al. provided a useful resource detailing the candidate signalling determinants of acquired TKI resistance; and reveals a therapeutic approach of inhibiting HSP90 function as a means of salvage therapy to overcome pazopanib and dasatinib resistance. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

0 | May 25 2019

Tajpara P et al. present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research. [Read the Full Post]

Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis

565 | May 24 2019

Chen G et al. provided a novel therapeutic strategy to optimize MK-1775 treatment efficiency in lung cancers. [Read the Full Post]

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial

1101 | May 21 2019

Rummel M et al. indicated that in combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. [Read the Full Post]

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success

417 | May 14 2019

Cazzaniga ME et al. proposed a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy. [Read the Full Post]

Dependency of Cholangiocarcinoma on Cyclin D-Dependent Kinase Activity

452 | May 13 2019

Sittithumcharee G et al. proposed that the CDK4/6-pRB pathway is a suitable therapeutic target for CCA treatment. This article is protected by copyright. All rights reserved. [Read the Full Post]

The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy

493 | May 09 2019

Zhou ZR et al. suggested that MK-8776increases human TNBC radiosensitivity by inhibiting irradiation-induced autophagy and that MK-8776 may be a potential agent in the radiosensitization of human TNBC. [Read the Full Post]

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

723 | May 07 2019

Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling

957 | May 06 2019

Kuusanmäki H et al. showed alternative approaches to inhibit STAT3 activity and suggest Hsp90 as a therapeutic target in lymphoproliferative disorders with constitutively active STAT3. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

719 | Apr 29 2019

Tajpara P et al. discovered that both drugs had a comparable efficacy for inhibiting HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir-resistant strains. To our knowledge, we present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research. [Read the Full Post]

In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R-roscovitine) in mantle cell lymphomas

523 | Apr 28 2019

Lacrima K et al. suggested that CYC202 is an active agent in MCL. The concomitant decrease of the phosphorylated and total forms of RNA polymerase II suggests that this could be the main mechanism mediating the biological effects of CYC202 in MCL cells. The drug might represent a new therapeutic agent in this lymphoma subtype. [Read the Full Post]

Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis

445 | Apr 18 2019

Jiang ZX et al. showed that roscovitine ameliorates EIU by effecting neutrophil apoptosis. Timely apoptosis of neutrophils may be an effective process to promote the amelioration of EIU. [Read the Full Post]

Prevention of Intraabdominal Adhesions: An Experimental Study Using Mitomycin-C and 4% Icodextrin

0 | Apr 16 2019

Urkan M et al. indicated that despite its potential for bone marrow toxicity, Mitomycin-C seems to effectively prevent adhesions. Further studies that prove an acceptable safety profile relating to this promising anti-adhesive agent are required before moving into clinical trials. [Read the Full Post]

CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells

946 | Apr 13 2019

Silva-Pavez E et al. suggested that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers. [Read the Full Post]

Mechanisms of U46619-induced contraction in mice intrarenal arteries

1297 | Mar 27 2019

Yan H et al. suggested that the U46619-induced contraction of mouse intrarenal arteries is mediated by Cav1.2 and SOC channel, through the activation of thromboxane-prostanoid receptors and its downstream signaling pathway. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

1298 | Mar 24 2019

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

Ten-Year and Beyond Follow-up After Treatment With Highly Purified Liquid-Injectable Silicone for HIV-Associated Facial Lipoatrophy: A Report of 164 Patients

507 | Mar 22 2019

Jones DH et al. showed that liquid-injectable silicone is an effective long-term treatment option for HIV-FLA. When injected in small quantities with the microdroplet serial puncture technique at monthly or greater intervals, optimal correction appears durable for more than 10 years. Adverse events consisted mostly of excess fibroplasia and were treatable. [Read the Full Post]

5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer

648 | Mar 22 2019

Morawska K et al. showed at a cycle 1, the 5-FU dose was calculated using patient's Body Surface Area (BSA) method. A blood sample was drawn on Day 2 to measure 5-FUconcentration. At cycle 2, the 5-FU dose was adjusted using a PK-guided dosing strategy targeting a plasma AUC range of 18-28 mg·h/L, based on cycle 1 concentration. Assessments of toxicity was performed at the beginning of every cycle. [Read the Full Post]

[Evolving 5-Fluorouracil Therapy to Achieve Enhanced Efficacy-Past and Current Efforts of Researchers]

534 | Mar 20 2019

Maehara Y et al. indicated that in the current standard treatment for gastrointestinal cancers, anticancer 5-FU derivatives serve as a platform for combination regimens with other cytotoxic agents or molecular- targeted drugs. To provide further improvements in anticancer therapy outcomes, novel molecular-targeted agents, immune checkpoint inhibitors, and other drugs are being developed, but 5-FU remains an attractive target that shows further potential for increased efficacy. In the future, the evolution of anticancer therapy with 5-FU derivatives is expected to continue via a variety of approaches. [Read the Full Post]

The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma

353 | Mar 18 2019

Ku BM et al. suggested that a combinational treatment with LY2835219 and mTOR inhibitor is a promising therapeutic approach for HNSCC. [Read the Full Post]

Combination treatment with docetaxel and histone deacetylase inhibitors downregulates androgen receptor signaling in castration-resistant prostate cancer

727 | Mar 06 2019

Park SE et al. suggested that docetaxel, in combination with HDACIs, suppressed the expression and nuclear translocation of AR-FL and AR-Vs and showed synergistic anti-proliferative effect in CRPC cells. This combination therapy may be useful for the treatment of patients with CRPC. [Read the Full Post]

Binding of the anticancer drug BI-2536 to human serum albumin. A spectroscopic and theoretical study

525 | Mar 01 2019

Fernández-Sainz J et al. showed that the main protein-drug interactions are of the van der Waals type although the presence of amide and ether groups in BI-2536 could also allow H-bonding with some residues in the subdomain IIA pocket. [Read the Full Post]

Tanespimycin as antitumor therapy

1155 | Feb 24 2019

Dimopoulos MA et al. showed that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A

1100 | Feb 22 2019

Cao ZF et al. provided information important for understanding the molecular mechanisms of SDHA mutations in tumors. [Read the Full Post]

ABCB1 Mediates Cabazitaxel-Docetaxel Cross-Resistance in Advanced Prostate Cancer

695 | Feb 16 2019

Lombard AP et al. suggested the potential in using combinations of antiandrogens with cabazitaxel for increased effect in treating advanced CRPC. [Read the Full Post]

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

808 | Feb 14 2019

Xu H et al. indicated these data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. [Read the Full Post]

Inhibition of Suicidal Erythrocyte Death by Volasertib

596 | Feb 04 2019

Al Mamun Bhuyan A et al. volasertib is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion and hyperosmotic shock, effects contrasting the stimulation of K562 cell apoptosis. [Read the Full Post]

BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity

607 | Feb 04 2019

Rudolph D et al. showed that with oral and i.v. routes of administration, the total weekly dose of BI 6727 is most relevant for efficacy, supporting the use of a variety of well-tolerated dosing schedules. [Read the Full Post]

Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer

816 | Feb 03 2019

Valle J et al. showed that as compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. [Read the Full Post]

Efficacy of the CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute lymphoblastic leukemia

575 | Feb 02 2019

Moharram SA et al. suggested that the CDK inhibitor dinaciclib is an active drug for T-ALL in the preclinical settings. [Read the Full Post]

Dinaciclib (SCH727965) inhibits the unfolded protein response through a CDK1- and 5-dependent mechanism

506 | Feb 02 2019

Nguyen TK et al. highlight a link between specific components of the cell-cycle regulatory apparatus (e.g., CDK1/5) and the cytoprotective IRE1/XBP-1s/Grp78 arm of the UPR that may be exploited therapeutically in UPR-driven malignancies. [Read the Full Post]

v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1

421 | Jan 27 2019

Ju X et al. found that Cyclin D1 serves as a transducer of v-Src-mediated induction of Trop2 ICD by enhancing abundance of the Trop2 proteolytic activation complex. [Read the Full Post]

27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells

765 | Jan 25 2019

Zhang L et al. not only found that ultra-high magnetic field can change the orientation and morphology of mitotic spindles, but also provided a tool to probe the role of spindle orientation and perturbation in developmental and cancer biology. [Read the Full Post]

Cisplatin is retained in the cochlea indefinitely following chemotherapy

590 | Jan 17 2019

Breglio AM et al. demonstrated long-term retention of cisplatin in the human cochlea, and they point to the stria vascularis as an important therapeutic target for preventing cisplatin ototoxicity. [Read the Full Post]

Efficacy of a bleomycin microneedle patch for the treatment of warts

642 | Jan 15 2019

Ryu HR et al. indicated the bleomycin microneedle patch can be an effective, convenient, and innovative treatment modality for warts. [Read the Full Post]

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm

1060 | Jan 08 2019

Barrio S et al. showed the combination of ruxolitinib with inhibitors that target these pathways has a strong synergistic effect, which may be due to decreased activation of the common effector, STAT5. [Read the Full Post]

Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models

765 | Jan 04 2019

Huang P et al. provided a strong rationale for clinical development of this combination in patients with advanced solid tumors. [Read the Full Post]

Inhibition of Chk1 with the small molecule inhibitor V158411 induces DNA damage and cell death in an unperturbed S-phase

592 | Dec 21 2018

Wayne J et al. identified two distinct classes of Chk1 inhibitors: those that induced a strong increase in γH2AX, pChk1 (S317) and pRPA32 (S4/S8) (including V158411, LY2603618 and ARRY-1A) and those that did not (including MK-8776 and GNE-900). [Read the Full Post]

PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells

0 | Dec 18 2018

Park GB et al. showed that characterization of the p110 isotypes of PI3K is critical for regulating cancer metastasis; LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

Leishmania donovani Aurora kinase: A promising therapeutic target against visceral leishmaniasis

802 | Dec 15 2018

Chhajer R et al. identified an Aurora kinase homolog in L. donovani implicated in cell-cycle progression, whose inhibition led to aberrant changes in cell-cycle progression and reduced viability. [Read the Full Post]

Therapeutic targeting of Polo-like kinase-1 and Aurora kinases in T-cell acute lymphoblastic leukemia

830 | Dec 13 2018

Spartà AM et al. indicated that PLK1 and AK inhibitors display the potential for being employed in innovative therapeutic strategies for improving T-ALL patient outcome. [Read the Full Post]

Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients

547 | Dec 06 2018

Prudencio M et al. concluded that increased RNA polymerase II activity in ALS/FTLD may lead to increased repetitive element transcript expression, a novel pathological feature of ALS/FTLD. [Read the Full Post]

Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold protein to polarize active Rac1 distribution

606 | Dec 02 2018

Kroon J et al. showed that flow induces Rac1 activity at the downstream side of the cell in a Trio-dependent manner and that Trio functions as a scaffold protein rather than a functional GEF under long-term flow conditions. [Read the Full Post]

Targeted inhibition of Polo-like kinase 1 by a novel small-molecule inhibitor induces mitotic catastrophe and apoptosis in human bladder cancer cells

509 | Nov 28 2018

Zhang Z et al. demonstrated of bladder cancer growth inhibition and dissemination using a pharmacological inhibitor of PLK1 provides new opportunities for future therapeutic intervention. [Read the Full Post]

RCN1 suppresses ER stress-induced apoptosis via calcium homeostasis and PERK-CHOP signaling

1154 | Nov 24 2018

Xu S et al. indicated that RCN1, a target of NF-κB, suppresses ER calcium release by binding to IP3R1 and decreases the UPR, thereby inhibiting ER stress-induced apoptosis. [Read the Full Post]

PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells.

1459 | Nov 23 2018

Park GB et al. found that LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance

0 | Nov 22 2018

Löschmann N et al. showed that ABCB1 expression represents the primary (sometimes exclusive) resistance mechanism in neuroblastoma cells with acquired resistance to SNS-032. [Read the Full Post]

The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine mast cell tumours in vitro

1438 | Nov 13 2018

Shiomitsu K et al. suggested the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy. [Read the Full Post]

Rac1 and Cdc42 Play Important Roles in Arsenic Neurotoxicity in Primary Cultured Rat Cerebellar Astrocytes

659 | Nov 12 2018

An Y et al. indicated that activations of Rac1 and Cdc42 play a very important role in arsenic neurotoxicity in rat cerebellum, providing a new insight into arsenic neurotoxicity. [Read the Full Post]

Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF Inhibitor Resistance of Melanoma, Pancreatic, and Non-Small Cell Lung Cancer Cells

902 | Nov 08 2018

The novel aspects of this study are the direct identification of serine biosynthesis as a critical mechanism of BRAF V600E inhibitor resistance and the first successful example of using gemcitabine + BRAFis in combination to kill previously drug-resistant cancer cells, creating the translational potential of pretreatment with gemcitabine prior to BRAFi treatment of tumor cells to reverse resistance within the mutational profile and the WT. [Read the Full Post]

Inhibitors of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) exert a strong anti-herpesviral activity

816 | Nov 01 2018

Hutterer C et al. concluded that DYRK signaling represents a promising target pathway for the development of novel anti-herpesviral strategies. [Read the Full Post]

DYRK1B blocks canonical and promotes non-canonical Hedgehog signaling through activation of the mTOR/AKT pathway

838 | Oct 31 2018

Singh R et al. showed that a pharmacological approach combining a DYRK1B antagonist with an mTOR/AKT inhibitor results in strong GLI1 targeting and in pronounced cytotoxicity in human pancreatic and ovarian cancer cells. [Read the Full Post]

Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells

0 | Oct 26 2018

Ma J et al. provided insight into the mechanism of action underlying the synergistic antileukemic activity of ATR inhibition in combination with cytarabine in AML. [Read the Full Post]

Curdione attenuates thrombin-induced human platelet activation: β1-tubulin as a potential therapeutic target

1645 | Oct 24 2018

Zhang D et al. indicated that β1-tubulin may be a potential target of curdione, which attenuates thrombin-induced human platelet activation. [Read the Full Post]

Reversible lysine-specific demethylase 1 antagonist HCI-2509 inhibits growth and decreases c-MYC in castration- and docetaxel-resistant prostate cancer cells

0 | Oct 18 2018

Gupta S et al. found that LSD1 inhibition with HCI-2509 decreases the c-MYC level in poorly differentiated prostate cancer cell lines and has a therapeutic potential in castration- and docetaxel-resistant prostate cancer. [Read the Full Post]

Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-κB signal pathways in thyroid carcinoma cells

3369 | Oct 07 2018

Kim SH et al. suggested that BIIB021 has a cytotoxic activity accompanied by regulation of hsp90 client proteins in thyroid carcinoma cells. Moreover, the synergism between BIIB021 and triptolide in induction of cytotoxicity is associated with the inhibition of PI3K/Akt/mTOR and NF-κB signal pathways, the underexpression of survivin and the activation of DNA damage response in thyroid carcinoma cells. [Read the Full Post]

WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

0 | Oct 03 2018

Zheng H et al. demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. [Read the Full Post]

CDK1-PDK1-PI3K/Akt signaling pathway regulates embryonic and induced pluripotency

1024 | Sep 18 2018

Wang XQ et al. demonstrated an essential role for the CDK1-PDK1-PI3K/Akt kinase signaling pathway in the regulation of self-renewal, differentiation, and somatic reprogramming, which provides a novel kinase cascade mechanism for pluripotency control and acquisition. [Read the Full Post]

P-TEFb Kinase Activity Is Essential for Global Transcription, Resumption of Meiosis and Embryonic Genome Activation in Pig

1021 | Sep 18 2018

Oqani RK et al. suggested that P-TEFb kinase activity is crucial for oocyte maturation, embryo development and regulation of RNA transcription in pig. [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

0 | Sep 02 2018

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [Read the Full Post]

Triptolide decreases expression of latency-associated nuclear antigen 1 and reduces viral titers in Kaposi's sarcoma-associated and herpesvirus-related primary effusion lymphoma cells

635 | Aug 30 2018

Long C et al. indicated that triptolide impairs the expression of LANA1 and shows antitumor activity against PEL in vitro and in vivo. Triptolide may be a potential agent for treatment of PEL. [Read the Full Post]

Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy

2566 | Aug 26 2018

Zhang P et al. suggested that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer. [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

0 | Aug 24 2018

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

0 | Aug 15 2018

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 | Aug 14 2018

Song M et al. indicated that small interfering RNA (siRNA)-based screening of ∼4800 druggable genes in 3-dimensional CSLC cultures in comparison to 2-dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for the following: survival of the CSLC population only, bulk-cultured population only, or both populations. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 | Aug 13 2018

Song M et al. provided a useful resource that can be exploited for the selective elimination of CSLCs.-Song, M., Lee, H., Nam, M.-H., Jeong, E., Kim, S., Hong, Y., Kim, N., Yim, H. Y., Yoo, Y.-J., Kim, J. S., Kim, J.-S., Cho, Y.-Y., Mills, G. B., Kim, W.-Y., Yoon, S. Loss-of-function screens of druggable targetome against cancer stem-like cells. [Read the Full Post]

CDK inhibitors suppress Th17 and promote iTreg differentiation, and ameliorate experimental autoimmune encephalomyelitis in mice

630 | Aug 06 2018

Yoshida H et al. suggested that CDK inhibitors modulate TGF-β-signaling pathways, which restore TGF-β-mediated suppression of IL-2 production, thereby modifying the Th17/iTreg balance. [Read the Full Post]

Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma

739 | Aug 04 2018

Mersch S et al. described for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies. [Read the Full Post]

Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways

970 | Jul 25 2018

Yang T et al. indicated that CuB interferes with multiple cellular pathways in MM cells. CuB thus represents a promising therapeutic tool for the treatment of MM. [Read the Full Post]

Oxidative stress induces mitotic arrest by inhibiting Aurora A-involved mitotic spindle formation

903 | Jul 24 2018

Wang GF et al. identified a mechanism by which ROS regulate mitotic progression and indicated a potential molecular target for the treatment of oxidative stress-related diseases. [Read the Full Post]

Downregulation of the PHLDA1 gene in IMR-32 neuroblastoma cells increases levels of Aurora A, TRKB and affects proteins involved in apoptosis and autophagy pathways

931 | Jul 24 2018

Durbas M et al. showed possible links of the protein to regulation of features of mitochondria and formation of autophagosomes. [Read the Full Post]

Effect of AKT3 expression on MYC- and caspase-8-dependent apoptosis caused by polo-like kinase inhibitors in HCT 116 cells

681 | Jul 18 2018

Nonomiya Y et al. indicated that MYC, caspase-8, P-GP, and AKT3 play critical roles in PLKi-induced apoptosis. Therefore, they are candidate biomarkers of the pharmacological efficacy of PLKis. [Read the Full Post]

Ribonucleotide Reductase Catalytic Subunit M1 (RRM1) as a Novel Therapeutic Target in Multiple Myeloma

732 | Jul 15 2018

Sagawa M et al. demonstrated that RRM1 is a novel therapeutic target in multiple myeloma in the preclinical setting and provide the basis for clinical evaluation of RRM1 inhibitor, alone or in combination with DNA-damaging agents, to improve patient outcome in multiple myeloma. [Read the Full Post]

Genome-wide localization of small molecules

735 | Jul 13 2018

Anders L et al. showed how Chem-seq can be combined with ChIP-seq to gain unique insights into the interaction of drugs with their target proteins throughout the genome of tumor cells. [Read the Full Post]

Transcription of HOTAIR is regulated by RhoC-MRTF-A-SRF signaling pathway in human breast cancer cells

849 | Jul 02 2018

He H et al. suggested that HOTAIR is regulated by the RhoC-MRTF-A-SRF signaling pathway in breast cancer cells. [Read the Full Post]

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

3526 | Jun 20 2018

Xi Y et al. supported the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. [Read the Full Post]

CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours

0 | Jun 19 2018

Costa-Cabral S et al. suggested that the KRAS/CDK1 interaction is a robust synthetic lethal effect worthy of further investigation. [Read the Full Post]

The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole

1509 | Jun 09 2018

Li L et al. showed that the activity of FLC against C. albicans biofilm formation in vitro is significantly enhanced when used in combination with HSP990. [Read the Full Post]

XL413, a cell division cycle 7 kinase inhibitor enhanced the anti-fibrotic effect of pirfenidone on TGF-β1-stimulated C3H10T1/2 cells via Smad2/4

700 | Jun 06 2018

Jin SF et al. demonstrated that pirfenidone inhibited proliferation, migration and differentiation of TGF-β1-stimulated C3H10T1/2 cells, which could be enhanced by Cdc7 inhibitor XL413, via Smad2/4. [Read the Full Post]

Calcineurin complex isolated from T-cell acute lymphoblastic leukemia (T-ALL) cells identifies new signaling pathways including mTOR/AKT/S6K whose inhibition synergize with calcineurin inhibition to promote T-ALL cell death

0 | May 31 2018

Tosello V et al. identified AKT inhibition as a novel promising drug combination to potentiate the pro-apoptotic effects of Cn inhibitors. [Read the Full Post]

Etoposide Induces Apoptosis in Activated Human Hepatic Stellate Cells via ER Stress

1467 | May 31 2018

Wang C et al. demonstrated that VP-16 exerts a proapoptotic effect on LX-2 cells and has an antifibrogenic effect on collagen deposition, suggesting a new strategy for the treatment of liver fibrosis. [Read the Full Post]

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

0 | May 30 2018

Kim HK et al. found that upregulation of mTOR/AKT pathway in sarcoma patient derived cells was considerably inhibited by the treatment of AZD2014 and BEZ235 with downregulation of AKT pathway (greater extent for BEZ235). [Read the Full Post]

Glucocorticoids Prevent Enterovirus 71 Capsid Protein VP1 Induced Calreticulin Surface Exposure by Alleviating Neuronal ER Stress

1426 | May 29 2018

Hu DD et al. identified VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications. [Read the Full Post]

Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis

1880 | May 21 2018

Franks SE et al. suggested that compounds selectively targeting AKT1 may prove more effective than compounds that inhibit all three AKT isoforms at least in the treatment of lung adenocarcinoma. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

6204 | May 20 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

Pharmacological Inhibition of PERK Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats Through the Activation of Akt

1364 | May 19 2018

Yan F et al. found that PERK might serve as a promising target for future therapeutic intervention. [Read the Full Post]

Mitotic entry: Non-genetic heterogeneity exposes the requirement for Plk1

833 | May 18 2018

Aspinall CF et al. discussed the implications for developing Plk1 inhibitors as chemotherapy agents and research tools. [Read the Full Post]

Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication

930 | May 13 2018

Kucharski TJ et al. determined that checkpoint kinase 1 and 2 signaling is important for apoptin regulation and is a likely feature of both tumor cells and host cells producing virus progeny. Inhibition of checkpoint signaling prevents apoptin toxicity in tumor cells and attenuates CAV replication, suggesting it may be a future target for antiviral therapy. [Read the Full Post]

Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells

0 | May 07 2018

Gopal SK et al. demonstrated for the first time that oncogenic cells undergoing EMT can communicate with endothelial cells via exosomes, and establish exosomal Rac1/PAK2 as angiogenic promoters that may function from early stages of the metastatic cascade. [Read the Full Post]

Phosphoproteome Profiling of SH-SY5y Neuroblastoma Cells Treated with Anesthetics: Sevoflurane and Isoflurane Affect the Phosphorylation of Proteins Involved in Cytoskeletal Regulation

884 | May 07 2018

Lee J et al. showed that anesthetics affect the phosphorylation of proteins involved in cytoskeletal remodeling pathways. [Read the Full Post]

Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice

862 | May 03 2018

Tu Z et al. demonstrated that Rac1 via P38 MAPK signaling ensures timely epithelial apoptotic death at postimplantation. Besides uncovering a potentially important molecule machinery governing uterine luminal integrity for embryo implantation, our finding has high clinical relevance, because Rac1 is essential for normal endometrial functions in women. [Read the Full Post]

Lipopolysaccharide and heat stress impair the estradiol biosynthesis in granulosa cells via increase of HSP70 and inhibition of smad3 phosphorylation and nuclear translocation

1574 | May 01 2018

Li H et al. suggested that LPS and heat stress could impair estradiol biosynthesis in GCs via increased HSP70 and indirect inhibition of Smad3 phosphorylation and nuclear translocation. [Read the Full Post]

P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest

860 | Apr 18 2018

Shamseddine AA et al. identifyd nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest. [Read the Full Post]

CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours

779 | Apr 17 2018

Costa-Cabral S et al. suggested that the KRAS/CDK1 interaction is a robust synthetic lethal effect worthy of further investigation. [Read the Full Post]

4-Hydroxy-2-nonenal induces apoptosis by activating ERK1/2 signaling and depleting intracellular glutathione in intestinal epithelial cells

1621 | Apr 08 2018

Ji Y et al. provided new insights into a functional role of MKP-1 in oxidative stress-induced cell death by regulating ERK1/2 MAP kinase in intestinal epithelial cells. [Read the Full Post]

ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance

896 | Apr 08 2018

Löschmann N et al. showed that ABCB1 expression represents the primary (sometimes exclusive) resistance mechanism in neuroblastoma cells with acquired resistance to SNS-032. Thus, ABCB1 inhibitors may increase the SNS-032 efficacy in ABCB1-expressing cells and prolong or avoid resistance formation. [Read the Full Post]

The Bub1-Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation

1146 | Apr 07 2018

Jia L et al. showed that human checkpoint kinase Bub1 not only directly phosphorylates Cdc20, but also scaffolds Plk1-mediated phosphorylation of Cdc20. [Read the Full Post]

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor

3382 | Apr 05 2018

Diculescu VC et al. indicated the danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained. [Read the Full Post]

Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib

1334 | Apr 05 2018

Wang W et al. demonstrated that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib. [Read the Full Post]

Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells

1053 | Mar 19 2018

Gopal SK et al. demonstrated for the first time that oncogenic cells undergoing EMT can communicate with endothelial cells via exosomes, and establish exosomal Rac1/PAK2 as angiogenic promoters that may function from early stages of the metastatic cascade. [Read the Full Post]

Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells

848 | Mar 17 2018

Gu Q et al. found the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells. [Read the Full Post]

Epothilone B induces apoptosis and enhances apoptotic effects of ABT-737 on human cancer cells via PI3K/AKT/mTOR pathway

0 | Mar 16 2018

Li YL et al. indicated that ABT-737 may be a pertinent sensitizer to epothilone B, and the strategy of combining epothilone B with ABT-737 appears to be an attractive option for overcoming the resistance and neurotoxicity of epothilone B. [Read the Full Post]

In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic Clinical Isolates

1412 | Mar 08 2018

AbdelKhalek A et al. suggested that certain rhodanine compounds may have potential use for the treatment of several multidrug-resistant Gram-positive bacterial infections. [Read the Full Post]

Late-stage inhibition of autophagy enhances calreticulin surface exposure

1370 | Mar 07 2018

Li DD et al. highlight the potential of the combined use of ER stress inducers and autophagy late-stage inhibitors to reestablish and strengthen both the CRT exposure and immunogenicity of chemotherapeutic agents induced death cells. [Read the Full Post]

The CDK9 Inhibitor Dinaciclib Exerts Potent Apoptotic and Antitumor Effects in Preclinical Models of MLL-Rearranged Acute Myeloid Leukemia

771 | Mar 06 2018

Baker A et al. highlight a new therapeutic approach to potentially overcome the resistance of MLL-rearranged AML to conventional chemotherapies and prompt further clinical evaluation of CDK inhibitors in AML patients harboring MLL fusion proteins. [Read the Full Post]

Inhibition of Skp2 sensitizes lung cancer cells to paclitaxel

897 | Mar 06 2018

Huang T et al. demonstrated that SKP2 positively regulates the gene expression of MAD2 through p27-CDKs-E2F1 signaling pathway and that inhibition of Skp2 sensitizes A549 and NCI-H1299 cells to paclitaxel, suggesting that small molecule inhibitors of Skp2 are potential agents for the treatment of lung cancer with upregulation of Skp2. [Read the Full Post]

Characterization of osimertinib (AZD9291)-resistant non-small cell lung cancer NCI-H1975/OSIR cell line

1642 | Mar 03 2018

Tang ZH et al. showed that EGFR could pose as one of the OSI-resistant mechanisms and navitoclax might be the candidate drug for OSI-resistant NSCLC patients. [Read the Full Post]

Phosphorylation-mediated activation of LDHA promotes cancer cell invasion and tumour metastasis

779 | Feb 26 2018

Jin L et al. demonstrated that LDHA phosphorylation and activation provide pro-invasive, anti-anoikis and pro-metastatic advantages to cancer cells, suggesting that Y10 phosphorylation of LDHA may represent a promising therapeutic target and a prognostic marker for metastatic human cancers. [Read the Full Post]

TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling

755 | Feb 22 2018

Wang B et al. revealed a GβL-ubiquitination-dependent switch that fine-tunes the dynamic organization and activation of the mTORC2 kinase under both physiological and pathological conditions. [Read the Full Post]

The effect of increased lipoproteins levels on the disposition of vincristine in rat

1389 | Feb 20 2018

Khalil HA et al. found that HL can potentiate another drug-drug or drug-disease interaction involving VCR warrants further studying and monitoring to ensure therapeutic safety and efficiency. [Read the Full Post]

Inhibition of mTOR suppresses human gallbladder carcinoma cell proliferation and enhances the cytotoxicity of 5-fluorouracil by downregulating MDR1 expression

0 | Feb 03 2018

Li Q, et al. found that dual mTORC1/mTORC2 inhibitors such as OSI-027 are promising therapeutic agents in combination with 5-FU for the treatment of human gallbladder cancer. [Read the Full Post]

Differentiation of induced pluripotent stem cell-derived neutrophil granulocytes from common marmoset monkey (Callithrix jacchus).

1968 | Jan 27 2018

Schrimpf C et al. indicated cj-iPSC-derived neutrophils bare high hopes in hematologic cell replacement therapy. They exhibit high morphologic similarity to native neutrophils and present neutrophil-specific surface antigens, antimicrobial proteins, and gene products yielding an auspicious approach for continuative experiments including tests in living animals. [Read the Full Post]

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

0 | Jan 22 2018

Cayrol F et al. showed that the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. [Read the Full Post]

TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2

670 | Jan 22 2018

Venkatesan S et al. suggested that Bcl-2 confers resistance to mTORC1/2 inhibitors in TP53 wild type GSCs and that combined inhibition of both mTORC1/2 and Bcl-2 is worthwhile to explore further in TP53 wild type glioblastomas, whereas in TP53 mutated glioblastomas dual mTORC1/2 inhibitors should be explored. [Read the Full Post]

Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism

777 | Jan 21 2018

Kuivanen S et al. provided the foundation for development of broad-spectrum cell-directed antivirals or their combinations for treatment of ZIKV and other emerging viral diseases. [Read the Full Post]

Efficacy of continuous EGFR-inhibition and role of Hedgehog in EGFR acquired resistance in human lung cancer cells with activating mutation of EGFR

67 | Jan 20 2018

Della Corte CM et al. found that EGFR-mutant NSCLC can benefit from continuous treatment with EGFR-inhibitors, indepenently from mechanisms of resistance [Read the Full Post]

Targeting high Aurora kinases expression as an innovative therapy for hepatocellular carcinoma

1318 | Jan 16 2018

Liu F et al. provided a solid evidence for SNS-314 as a potential targeted therapy, and a proof-of-concept evidence for a possible combined therapy of SNS-314 plus Hippo pathway inhibitors on HCC. [Read the Full Post]

CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1

771 | Jan 15 2018

Sathe A et al. provided preclinical evidence that CDK4/6 inhibition is a potential therapeutic strategy for retinoblastoma positive bladder cancer that probably acts by negatively regulating retinoblastoma transcription. [Read the Full Post]

AKT is indispensable for coordinating Par-4/JNK cross talk in p21 downmodulation during ER stress

1435 | Jan 10 2018

Rasool RU et al. found that 3-AWA inhibits colorectal tumor growth and formation of colorectal polyps at a tolerable dose, similar to the first-line drug for colorectal cancer-5-fluorouracil. [Read the Full Post]

Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling

1726 | Jan 04 2018

Dong HM et al. suggested that eHsp90α is a potential therapeutic target for treatment of asthma. [Read the Full Post]

Cathelicidin-WA Improves Intestinal Epithelial Barrier Function and Enhances Host Defense against Enterohemorrhagic Escherichia coli O157:H7 Infection

906 | Dec 31 2017

Yi H et al. showed that CWA attenuated EHEC-induced inflammation, intestinal epithelial barrier damage, and microbiota disruption in the intestine of mice, suggesting that CWA may be an effective therapy for many intestinal diseases. [Read the Full Post]

Organ-specific efficacy of HSP90 inhibitor in multiple-organ metastasis model of chemorefractory small cell lung cancer

1003 | Dec 28 2017

Takeuchi S et al. suggested that therapeutic effects of HSP90 inhibitors may be organ-specific and should be carefully monitored in SCLC clinical trials. [Read the Full Post]

BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy

1301 | Dec 27 2017

Slone WL et al. suggested that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response. [Read the Full Post]

Lenvatinib enhances the antitumor effects of paclitaxel in anaplastic thyroid cancer

1435 | Dec 22 2017

Jing C et al. suggested that lenvatinib/paclitaxel combination may be a promising candidate therapeutic strategy for ATC. [Read the Full Post]

MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity

1325 | Dec 14 2017

Chen X et al. showed that mitotic phosphorylation-deficient mutant MST2-S385A possesses higher activity in suppressing cell proliferation and anchorage-independent growth in vitro and tumorigenesis in vivo. Together, our findings reveal a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis. [Read the Full Post]

Rigosertib as a selective anti-tumor agent can ameliorate multiple dysregulated signaling transduction pathways in high-grade myelodysplastic syndrome

975 | Dec 12 2017

Xu F et al. indicated that rigosertib is a selective and promising anti-tumor agent that could ameliorate multiple dysregulated signaling transduction pathways in high-grade MDS. [Read the Full Post]

Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity

1363 | Dec 11 2017

Maimaiti Y, et al. indicated that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer. [Read the Full Post]

The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy

1113 | Dec 11 2017

Zhou ZR et al. suggested that MK-8776 increases human TNBC radiosensitivity by inhibiting irradiation-induced autophagy and that MK-8776 may be a potential agent in the radiosensitization of human TNBC. [Read the Full Post]

Antitumor action of CDK inhibitor LS-007 as a single agent and in combination with ABT-199 against human acute leukemia cells

848 | Dec 05 2017

Xie S et al. showed that CDK inhibitor LS-007 potently inhibits the established human AL cell lines and primary AL blasts, and it also shows remarkable synergy with Bcl-2 inhibitor ABT-199. [Read the Full Post]

CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation

0 | Dec 02 2017

Liu Y et al. identified a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer. [Read the Full Post]

HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death

1857 | Nov 29 2017

Jacobsen AV et al. implicated HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90's previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3. [Read the Full Post]

The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms

2055 | Nov 25 2017

Paraiso KH et al.showed that HSP90 inhibition may be a highly effective strategy at managing the diverse array of resistance mechanisms being reported to BRAF inhibitors and appears to be more effective at restoring BIM expression and downregulating Mcl-1 expression than combined MEK/PI3K inhibitor therapy. [Read the Full Post]

Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma

1846 | Nov 24 2017

Meng J et al. investigated the correlation between Hsp90β expression and CD31+ endothelial cell-dependent vessel density. [Read the Full Post]

WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

1132 | Nov 19 2017

demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. Thus targeting DNA replication and G2-M cell cycle checkpoint simultaneously by cisplatin and WEE1 inhibition is promising for TNBCs treatment, and for overcoming their cisplatin resistance. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Nov 14 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

1170 | Nov 11 2017

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [Read the Full Post]

Molecular mechanism of G1 arrest and cellular senescence induced by LEE011, a novel CDK4/CDK6 inhibitor, in leukemia cells

894 | Nov 08 2017

Tao YF et al. demonstrated for the first time that LEE011 treatment results in inhibition of cell proliferation and induction of G1 arrest and cellular senescence in leukemia cells. LncRNA microarray analysis showed differentially expressed mRNAs and lncRNAs in LEE011-treated HL-60 cells and we demonstrated that LEE011 induces cellular senescence partially through downregulation of the expression of MYBL2. These results may open new lines of investigation regarding the molecular mechanism of LEE011 induced cellular senescence. [Read the Full Post]

Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors

955 | Nov 07 2017

Zhang M et al. identified AJUBA, SMAD4 and RAS mutations as potential candidate biomarkers of response of HNSCC to treatment with these mitotic inhibitors. [Read the Full Post]

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

0 | Nov 06 2017

Isono M et al. showed that AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy. [Read the Full Post]

BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

1284 | Nov 02 2017

Rasmussen RD et al. proposed that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM. [Read the Full Post]

Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy

0 | Oct 29 2017

Noguchi K et al. suggested that AKT3 could repress the antiproliferative effects of AURKi, with a novel activity particularly suppressing the aneuploidy induction. [Read the Full Post]

Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells

1063 | Oct 26 2017

Bista R et al. provided evidence that DSF/Cu2+ overcomes Ara-C and BTZ resistance in cell lines from DS-AMKL patients. A novel mutation underlying BTZ resistance was detected that may identify BTZ-resistant patients, who may not benefit from treatment with CFZ or Ara-C, but may be responsive to DSF/Cu2+. Our findings support the clinical development of DSF/Cu2+ as a less toxic efficacious treatment approach in patients with relapsed/refractory DS-AMKL. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

2520 | Oct 16 2017

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype

1436 | Oct 14 2017

Schultz MJ et al. found that ST6Gal-I induced expression of the key tumor-promoting transcription factors, Sox9 and Slug [Read the Full Post]

Expression and clinical significance of Wee1 in colorectal cancer

0 | Oct 12 2017

Egeland EV et al. indicated that other tumor types might be better suited for further development of Wee1 inhibitors. [Read the Full Post]

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

0 | Oct 11 2017

Chang X et al. reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. [Read the Full Post]

Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

0 | Oct 06 2017

Hain KO et al. demonstrated that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. [Read the Full Post]

STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

1917 | Oct 04 2017

Song Z et al. suggested that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia. [Read the Full Post]

PARP inhibitor increases chemosensitivity by upregulating miR-664b-5p in BRCA1-mutated triple-negative breast cancer

1032 | Oct 02 2017

Song W et al. showed that miR-664b-5p functions as a tumour suppressor and has an important role in the regulation of PARP inhibitors to increase chemosensitivity by targeting CCNE2. This may be one of the possible mechanisms by which PARP inhibitors increase chemosensitivity in BRCA1-mutated TNBC. [Read the Full Post]

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

3051 | Sep 30 2017

Here Han T et al. showed that indisulam promotes the recruitment of RBM39 (RNA binding motif protein 39) to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation. [Read the Full Post]

In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment

0 | Sep 27 2017

Perez-Peña J et al. demonstrated the antitumor effect of this new family of compounds in TNBC, paving the way for its future clinical development. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Sep 26 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

2062 | Sep 25 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib

1822 | Sep 22 2017

Areeb Z et al. showed that carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme. [Read the Full Post]

The Enhancement of Radiation Sensitivity in Nasopharyngeal Carcinoma Cells via Activation of the Rac1/NADPH Signaling Pathway

1097 | Sep 15 2017

Wang C et al. indicate that the Rac1 protein may be the key target involved in the radiosensitization of nasopharyngeal carcinoma cells. [Read the Full Post]

Hyperthermia reduces migration of osteosarcoma by suppression of autocrine motility factor

2063 | Sep 09 2017

Nakajima K et al. indicated hyperthermia reduced AMF expression and tumor cell motility via HSP27 and may therefore be applied as osteosarcoma treatment. [Read the Full Post]

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

2339 | Sep 09 2017

Thompson JM et al. suggested that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [Read the Full Post]

Targeted knockdown of polo-like kinase 1 alters metabolic regulation in melanoma

1144 | Aug 22 2017

Gutteridge RE et al. suggested that PLK1 may be an important regulator of metabolism maintenance in melanoma cells. [Read the Full Post]

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

2051 | Aug 20 2017

Isono M et al. showed that AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy. [Read the Full Post]

Plasmonic nanocarrier grid-enhanced Raman sensor for studies of anticancer drug delivery

1552 | Aug 20 2017

Kurzątkowska K et al. demonstrated that the proposed nanocarrier SERS sensor can be utilized to investigate attachment of targeting ligands to nanocarriers (attachment of folic acid ligand recognized by folate receptors of cancer cells is described). Further testing of the nanocarrier SERS sensor involved drug release induced by lowering pH and increasing GSH levels, both occurring in cancer cells. The proposed sensor can be utilized for a variety of drugs and targeting ligands, including those which are Raman inactive, since the linkers can act as the Raman markers, as illustrated with mercaptobenzoic acid and para-aminothiophenol. [Read the Full Post]

Nuclear PTEN interferes with binding of Ku70 at double-strand breaks through post-translational poly(ADP-ribosyl)ation

1149 | Aug 14 2017

Guan J, et al. provided contributes to understanding the effect of PTEN in repair of DSB and using defined anti-tumor DSB drugs to treat tumor cells with aberrant PTEN. [Read the Full Post]

HOXC10 Expression Supports the Development of Chemotherapy Resistance by Fine Tuning DNA Repair in Breast Cancer Cells

0 | Aug 04 2017

Sadik H et al. showed that HOXC10 facilitates, but is not directly involved in DNA damage repair mediated by HR. [Read the Full Post]

Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy

1760 | Jul 31 2017

Noguchi K et al. suggests that AKT3 could repress the antiproliferative effects of AURKi, with a novel activity particularly suppressing the aneuploidy induction. [Read the Full Post]

Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells

1575 | Jul 30 2017

Katsha A et al. indicated that AURKA plays an important role in the activation of EIF4E and cap-dependent translation. Targeting the AURKA-EIF4E-c-MYC axis using alisertib is a novel therapeutic strategy that can be applicable for everolimus-resistant tumors and/or subgroups of cancers that show overexpression of AURKA and activation of EIF4E and c-MYC. [Read the Full Post]

Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors

1203 | Jul 23 2017

Zhang M et al. identified AJUBA, SMAD4 and RAS mutations as potential candidate biomarkers of response of HNSCC to treatment with these mitotic inhibitors. [Read the Full Post]

Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells

0 | Jul 19 2017

Wu X et al. demonstrated that GP130/STAT3 signaling contributes to the resistance of these drugs in rhabdomyosarcoma cells. They also suggested a potentially novel cancer therapeutic strategy using the combination of inhibitors of GP130/STAT3 signaling with doxorubicin, cisplatin, or AZD6244 for rhabdomyosarcoma treatments. [Read the Full Post]

MiR-193a-5p Targets the Coding Region of AP-2α mRNA and Induces Cisplatin Resistance in Bladder Cancers

2742 | Jul 18 2017

Zhou J et al. concluded that miR-193a-5p induced cisplatin resistance by repressing AP-2α expression in bladder cancer cells. [Read the Full Post]

The RNA-Binding Proteins Zfp36l1 and Zfp36l2 Enforce the Thymic β-Selection Checkpoint by Limiting DNA Damage Response Signaling and Cell Cycle Progression

2627 | Jul 16 2017

Vogel KU et al. showed that in addition to controlling the timing of proliferation at β-selection, posttranscriptional control by Zfp36l1/l2 limits DNA damage responses, which are known to promote thymocyte differentiation. Zfp36l1/l2 therefore act as posttranscriptional safeguards against chromosomal instability and replication stress by integrating pre-TCR and IL-7 signaling with DNA damage and cell cycle control. [Read the Full Post]

METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion

2091 | Jul 16 2017

Zhang Z et al. identified METTL13 as a tumor suppressor and might provide promising approaches for bladder cancer treatment and prevention. [Read the Full Post]

Identification of DYRK1B as a substrate of ERK1/2 and characterisation of the kinase activity of DYRK1B mutants from cancer and metabolic syndrome

1149 | Jul 13 2017

Ashford AL et al. showed that DYRK1B is a novel ERK2 substrate, uncovering new links between two kinases involved in cell fate decisions. Finally, we show that DYRK1B mutants that have recently been described in cancer and metabolic syndrome exhibit normal or reduced intrinsic kinase activity. [Read the Full Post]

Ras oncogene-independent activation of RALB signaling is a targetable mechanism of escape from NRAS(V12) oncogene addiction in acute myeloid leukemia

1247 | Jul 09 2017

Pomeroy EJ et al. demonstrated that Ras oncogene-independent activation of RALB signaling is a therapeutically targetable mechanism of escape from NRAS oncogene addiction in AML. [Read the Full Post]

A cyclin-dependent kinase inhibitor, dinaciclib in preclinical treatment models of thyroid cancer

1433 | Jul 09 2017

Lin SF et al. findings support dinaciclib as a potential drug for further studies in clinical trials for the treatment of patients with refractory thyroid cancer. [Read the Full Post]

Phosphorylation of Astrin Regulates Its Kinetochore Function

0 | Jul 01 2017

Chung HJ et al. revealed a regulatory circuit for protein targeting to KTs that controls the KT composition change of stable spindle attachment and chromosome [Read the Full Post]

Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth

1864 | Jun 28 2017

Parra K et al. proved Sequential therapy of anti-CTLA-4 followed by gemcitabine is effective in chemotherapy-naive tumours, although tumour relapses can occur, in some cases accompanied by the development of spontaneous metastases. [Read the Full Post]

Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines

5791 | Jun 18 2017

Li ZY et al. showed that RGFP109, an HDAC inhibitor, in combination with TMZ may be a therapeutic candidate for patients with temozolomide-resistant GBM. [Read the Full Post]

PARP Inhibitor Activity Correlates with SLFN11 Expression and Demonstrates Synergy with Temozolomide in Small Cell Lung Cancer

1381 | Jun 18 2017

Lok BH et al. found that SLFN11 is a relevant predictive biomarker of sensitivity to PARP inhibitor monotherapy in SCLC and we identify combinatorial therapy with TMZ as a particularly promising therapeutic strategy that warrants further clinical investigation. [Read the Full Post]

Cyclin D1 depletion induces DNA damage in mantle cell lymphoma lines

1202 | Jun 09 2017

Mohanty S et al. had an important implication for CCND1 as a potential therapeutic target in MCL patients who are refractory to standard chemotherapy. [Read the Full Post]

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

3295 | Jun 06 2017

Guo SC et al. provided evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction. [Read the Full Post]

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

0 | Jun 05 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α

4624 | Jun 04 2017

Han T et al. found that CD437 is a retinoid-like small molecule that selectively induces apoptosis in cancer cells, but not in normal cells, through an unknown mechanism. [Read the Full Post]

The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line

2011 | Jun 02 2017

Wang J et al. found that serine/threonine AK inhibition, essentially with VX-680, could be a promising, specific therapeutic tool for eradicating metastases in adrenocortical tissue. [Read the Full Post]

Reversible lysine-specific demethylase 1 antagonist HCI-2509 inhibits growth and decreases c-MYC in castration- and docetaxel-resistant prostate cancer cells

1346 | May 30 2017

Gupta S et al. found that LSD1 inhibition with HCI-2509 decreases the c-MYC level in poorly differentiated prostate cancer cell lines and has a therapeutic potential in castration- and docetaxel-resistant prostate cancer. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

0 | May 22 2017

Massa MG et al. provided an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery. [Read the Full Post]

Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells

0 | May 12 2017

Liu Y et al. suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. [Read the Full Post]

Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells

3546 | Apr 30 2017

Liu Y et al. suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. [Read the Full Post]

Enhancing glioblastoma cell sensitivity to chemotherapeutics: a strategy involving survivin gene silencing mediated by gemini surfactant-based complexes

0 | Apr 26 2017

Cruz RQ et al showed that survivin downregulation combined with administration of the chemotherapeutic agents temozolomide or etoposide resulted in a synergistic cytotoxic effect, thus revealing to be a promising strategy to reduce the chemotherapeutic doses for GBM treatment. [Read the Full Post]

Electrochemical biosensor for protein kinase A activity assay based on gold nanoparticles-carbon nanospheres, phos-tag-biotin and β-galactosidase

3084 | Apr 21 2017

Zhou Y et al. found the fabricated biosensor can be applied to detect PKA in human normal gastricepithelial cell line and human gastric carcinoma cell line with satisfactory results. [Read the Full Post]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

2807 | Apr 18 2017

Yi H et al found weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells.

3564 | Apr 17 2017

Choi JI et al found that addition of BX795 or CCT128930 to inhibit pS6 (S240/S244) or pS6 (S235/S236) restricted the compensatory adaptive response to paclitaxel in HeyA8 and SKOV3 cells. These inhibitors increased the efficacy of paclitaxel in reducing cancer cell viability. [Read the Full Post]

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

0 | Apr 06 2017

Hsu YC et al showed that activation of AurA kinase through FGF1/FGFR signaling axis sustains the stem cell characteristics of GBM cells. [Read the Full Post]

A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition

2479 | Apr 06 2017

Kim H et al. demonstrated that CX-4945 is a potent DYRK1A inhibitor and also suggested that it has therapeutic potential for DYRK1A-associated diseases. [Read the Full Post]

A Repurposing Strategy for Hsp90 Inhibitors Demonstrates Their Potency against Filarial Nematodes

1 | Mar 27 2017

Gillan V et al provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Linifanib (ABT-869) Potentiates the Efficacy of Chemotherapeutic Agents through the Suppression of Receptor Tyrosine Kinase-Mediated AKT/mTOR Signaling Pathways in Gastric Cancer

1258 | Mar 23 2017

Chen J et al. suggested that the addition of ABT-869 to traditional chemotherapies may be a promising strategy for the treatment of human gastric cancer. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

2172 | Mar 14 2017

Huyan T et al. suggested that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Mar 13 2017

Sampson VB et al suggested that potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Structural Insights into the Pharmacophore of Vinca Domain Inhibitors of Microtubules

1452 | Mar 03 2017

Wang Y et al. found that the rational design of novel vinca domain ligands and may facilitate the development of microtubule inhibitors with high specificity, affinity, and efficiency as payloads for ADCs in cancer therapy. [Read the Full Post]

Novel pyrimidine-2,4-diamine derivative suppresses the cell viability and spindle assembly checkpoint activity by targeting Aurora kinases

1191 | Mar 02 2017

Salmela AL et al. suggested that this new pharmacophore possesses interesting anticancer properties that could be exploited in development of mitosis-targeting therapies. [Read the Full Post]

Activation of Fibroblast-like Synoviocytes in Regulates Migration, Invasion, and Protein Inhibitor of Activated STAT3 Rheumatoid Arthritis

1327 | Mar 01 2017

Lao M, et al.'s observations suggest that PIAS3 suppression may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, and activation. [Read the Full Post]

Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance

0 | Feb 28 2017

Ma HT, et al.'s results provide a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. [Read the Full Post]

Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeuticmediated cell death

1893 | Feb 27 2017

Chen H, et al.'s results establish the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. [Read the Full Post]

CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1

1179 | Feb 26 2017

Sathe A, et al. provide preclinical evidence that CDK4/6 inhibition is a potential therapeutic strategy for retinoblastoma positive bladder cancer that probably acts by negatively regulating retinoblastoma transcription. [Read the Full Post]

Epothilone B induces apoptosis and enhances apoptotic effects of ABT-737 on human cancer cells via PI3K/AKT/mTOR pathway

1478 | Feb 25 2017

These data indicate that ABT-737 may be a pertinent sensitizer to epothilone B, and the strategy of combining epothilone B with ABT-737 appears to be an attractive option for overcoming the resistance and neurotoxicity of epothilone B. [Read the Full Post]

Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells

3065 | Feb 24 2017

Gu Q et al.'s findings have elucidated the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells. [Read the Full Post]

Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes

0 | Feb 14 2017

Gu N, et al.'s findings suggest that palmitate increases musclin gene expression via the activation of the PERK signaling pathway in C2C12 myotubes. [Read the Full Post]

Epithelial-Mesenchymal Transition Predicts Polo-Like Kinase 1 Inhibitor-Mediated Apoptosis in Non-Small Cell Lung Cancer

1583 | Feb 13 2017

In Ferrarotto R, et al.'s first reported large-scale integrated analysis of PLK1 inhibitor sensitivity, we demonstrated that EMT leads to PLK1 inhibition sensitivity of NSCLC cells. Our findings have important clinical implications for mesenchymal NSCLC, a significant subtype of the disease that is associated with resistance to currently approved targeted therapies. [Read the Full Post]

RNA polymerase I transcription is modulated by spatial learning in different brain regions.

1479 | Feb 08 2017

Capitano F, et al.'s results suggest that de novo rRNA transcription is a necessary step for spatial memory consolidation and that after learning it occurs in several brain regions with a complex spatio-temporal dynamic. This article is protected by copyright. All rights reserved. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Feb 04 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

4849 | Jan 29 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Jan 26 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

2259 | Jan 22 2017

Huyan T, et al.'s findings suggest that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Jan 21 2017

In Sampson VB, et al.'s summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death

2036 | Jan 15 2017

Chen H et al. found the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. [Read the Full Post]

Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance

2103 | Jan 15 2017

Ma HT et al. provided a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. [Read the Full Post]

CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1

0 | Jan 13 2017

Sathe A, et al. provide preclinical evidence that CDK4/6 inhibition is a potential therapeutic strategy for retinoblastoma positive bladder cancer that probably acts by negatively regulating retinoblastoma transcription. [Read the Full Post]

Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes

1927 | Jan 07 2017

Gu N et al. suggested that palmitate increases musclin gene expression via the activation of the PERK signaling pathway in C2C12 myotubes. [Read the Full Post]

Epithelial-Mesenchymal Transition Predicts Polo-Like Kinase 1 Inhibitor-Mediated Apoptosis in Non-Small Cell Lung Cancer

1417 | Jan 06 2017

The study of Ferrarotto R, et al. demonstrated that EMT leads to PLK1 inhibition sensitivity of NSCLC cells. Our findings have important clinical implications for mesenchymal NSCLC, a significant subtype of the disease that is associated with resistance to currently approved targeted therapies. [Read the Full Post]

RNA polymerase I transcription is modulated by spatial learning in different brain regions.

0 | Jan 03 2017

J Neurochem's results suggested that de novo rRNA transcription is a necessary step for spatial memory consolidation and that after learning it occurs in several brain regions with a complex spatio-temporal dynamic. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

2619 | Jan 01 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

Phosphorylation of Astrin Regulates Its Kinetochore Function

0 | Dec 26 2016

Chung HJ et al. revealed a regulatory circuit for protein targeting to KTs that controls the KT composition change of stable spindle attachment and chromosome integrity. [Read the Full Post]

Phosphorylation of Astrin Regulates Its Kinetochore Function

1467 | Dec 23 2016

Chung HJ et al. revealed a regulatory circuit for protein targeting to KTs that controls the KT composition change of stable spindle attachment and chromosome integrity. [Read the Full Post]

HOXC10 Expression Supports the Development of Chemotherapy Resistance by Fine Tuning DNA Repair in Breast Cancer Cells

1402 | Dec 11 2016

Sadik H et al. found that inhibitors of CDK7 reverse HOXC10-mediated drug resistance in cultured cells. Blocking HOXC10 function, therefore, presents a promising new strategy to overcome chemotherapy resistance in breast cancer. [Read the Full Post]

The Enhancement of Radiation Sensitivity in Nasopharyngeal Carcinoma Cells via Activation of the Rac1/NADPH Signaling Pathway

0 | Dec 01 2016

Wang C, et al. found that the activated Rac1/NADPH pathway combined with radiation can increase the radiosensitivity of nasopharyngeal carcinoma cells, and the Rac1/NADPH pathway may be the signaling pathway involved in the radiosensitization process. [Read the Full Post]

In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment

2018 | Nov 26 2016

Perez-Peña J et al. demonstrated the antitumor effect of this new family of compounds in TNBC, paving the way for its future clinical development. [Read the Full Post]

Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

2230 | Nov 23 2016

Hain KO et al. demonstrated that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. [Read the Full Post]

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

2113 | Nov 17 2016

Chang X et al. revealed that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. [Read the Full Post]

Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer

2236 | Nov 17 2016

Ju HQ et al. revealed a novel regulatory mechanism for Nampt in PDAC and suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. [Read the Full Post]

Expression and clinical significance of Wee1 in colorectal cancer

1787 | Nov 16 2016

The lack of clinical significance of Wee1 expression could indicate that other tumor types might be better suited for further development of Wee1 inhibitors. [Read the Full Post]

The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype

2018 | Nov 13 2016

Schultz MJ et al. highlighted a previously unrecognized role for a specific glycosyltransferase in driving a CSC state. [Read the Full Post]

Ajuba Phosphorylation by CDK1 Promotes Cell Proliferation and Tumorigenesis

2485 | Nov 04 2016

Chen X et al. revealed a previously unrecognized mechanism for Ajuba regulation in mitosis and its role in tumorigenesis. [Read the Full Post]

The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α

2234 | Nov 01 2016

The discovery of POLA1 as the direct anticancer target for CD437 has the potential to catalyze the development of CD437 into an anticancer therapeutic. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

4360 | Oct 19 2016

[Read the Full Post]

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells

2194 | Sep 19 2016

[Read the Full Post]

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

2342 | Sep 09 2016

Hsu YC et al. identified a novel mechanism for the malignancy of GBM, which could be a potential therapeutic target for GBM. [Read the Full Post]

Protein Inhibitor of Activated STAT3 Regulates Migration, Invasion, and Activation of Fibroblast-like Synoviocytes in Rheumatoid Arthritis

1554 | Sep 01 2016

Lao M, et al. suggested that PIAS3 suppression may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, and activation. [Read the Full Post]

The role of nuclease FAN1 in DNA crosslink repair in Arabidopsis thaliana

2825 | Mar 26 2015

Herrmann et al. demonstrated that FAN1 homolog is present in plants and is proved to be involved in Arabidopsis thaliana CL repair. [Read the Full Post]

CY190602, a novel DNA/HDAC dual-targeting drug with enhanced anti-cancer potency

9867 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

10589 | Feb 10 2015

Shi et al. reported clinical proteasome inhibitor enable to block proplatelet formation by megakaryocytes in human and mouse model. [Read the Full Post]

Recently identified CHEK2 Y390C mutation facilitates early breast cancer development

6825 | Feb 05 2015

Wang et al. identified a missense variant Y390C of CHEK2 that related to tumorigenesis in high-risk breast cancer patients. [Read the Full Post]

A protocol for human pluripotent stem cell differentiation into endoderm related cells

7559 | Feb 02 2015

Diekmann et al. showed a detailed protocol started from a defined cell number of dispersed single cells of three different human ESC lines, and one human iPSC line. [Read the Full Post]

The distribution of primary cilia in the mouse embyo

5010 | Jan 27 2015

Bangs et al. demonstrate the time and location that primary cilia appear in the mouse embryo. [Read the Full Post]

Cep68 act as an important linker protein of centrosomes and centriole disengagement

5094 | Dec 26 2014

Pagan et al. indentified the important roles of Cep68 and other related factors during the disengagement of centrosomes and entrioles. [Read the Full Post]

MeCP2 S421 phosphorylation mediates neurogenesis via Notch signaling pathway

8782 | Dec 04 2014

Li et al. identified the Notch signaling is involved in the regulation of MeCP2 S421 phosphorylation other than neuronal activity. [Read the Full Post]

Quickly switching of spindle checkpoint states is due to negative feedback at kinetochrores

4544 | Nov 27 2014

Nijenhuis et al. found this phenomenon arises due to localized negative feedback of spindle assemble checkpoint (SAC) signal, which ensure kinetochres switch SAC signalling OFF rapidly. [Read the Full Post]

ERK/Cdk5 axis regulates diabetes-related PPARγ phosphorylation

8175 | Nov 21 2014

Recently, Banks et al. discovered that ERK/Cdk5 axis is involved in regulation PPARγ activities, and the inhibition of ERK and MEK leads to the improvement of insulin resistance. [Read the Full Post]

Is it really that nonselective inhibitors have no future in clinical study

2494 | Apr 01 2014

R547 is a potent ATP-competitive inhibitor of CDK1/2/4 with Ki of 2 nM/3 nM/1 nM. It is less potent to CDK7 and GSK3α/β, while inactive to other kinases. [Read the Full Post]

Y27632 is a biochemical tool used in the study of the ROCK

5872 | Mar 05 2014

Y-27632 2HCl inhibits ROCK-II while displaying little activity against PKC. [Read the Full Post]

Here we assess the in vitro and in vivo anti MM activity of MLN8237

2853 | Feb 26 2014

MLN8237 shows >200-fold higher selectivity for Aurora A than the structurally related Aurora B with an IC50 of 396.5 nM, and does not have any significant activity against 205 other kinases. [Read the Full Post]

Roscovitine is an experimental drug in the family

2404 | Feb 25 2014

Roscovitine (Seliciclib, CYC202) is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. [Read the Full Post]

Adriamycin is an anti cancer chemotherapy drug

0 | Jan 27 2014

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis. [Read the Full Post]

Y 27632 is available in a 5 mg format and has been optimized

5560 | Jan 17 2014

Y-27632 2HCl is a selective ROCK1 (p160ROCK) inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

R547 is a potent and selective ATP competitive CDK inhibitor

2451 | Jan 16 2014

R547 is a potent ATP-competitive inhibitor of CDK1/2/4 with Ki of 2 nM/3 nM/1 nM. It is less potent to CDK7 and GSK3α/β, while inactive to other kinases. [Read the Full Post]

Adriamycin is photosensitive and containers

2895 | Jan 10 2014

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis. [Read the Full Post]

Y 27632 is a biochemical tool used in the study of the rho associated protein kinase

5643 | Jan 10 2014

Y-27632 2HCl is a selective ROCK1 inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

Roscovitine is an experimental drug candidate in the family

2621 | Jan 07 2014

Roscovitine is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. [Read the Full Post]

NU7441 is a potent novel DNA PK inhibitor

2876 | Dec 26 2013

NU7441 is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM and also inhibits PI3K with IC50 of 5 μM. [Read the Full Post]

R547 is a potent ATP competitive inhibitor of CDK

2637 | Dec 10 2013

R547 identified as a diaminopyrimidine compound, which is a potent and selective ATP-competitive CDK inhibitor. [Read the Full Post]

Adriamycin is an anti cancer chemotherapy drug

3148 | Dec 02 2013

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis. [Read the Full Post]

Decitabine is a drug for the treatment of myelodysplastic syndromes

3098 | Nov 22 2013

Decitabine is a potent inhibitor of DNA methylation with IC50 of 438 nM and 4.38 nM in HL-60 and KG1a cells, respectively. [Read the Full Post]

Thiazovivin helps in promoting human embryonic stem cell

5364 | Nov 22 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

Roscovitine is a cell permeable reversible selective inhibitor

2771 | Nov 21 2013

Roscovitine (Seliciclib, CYC202) is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. It shows little effect on CDK4/6. [Read the Full Post]

Roscovitine is an experimental drug candidate in the family of pharmacological

2933 | Nov 19 2013

Roscovitine (Seliciclib, CYC202) is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. It shows little effect on CDK4/6. [Read the Full Post]

Thiazovivin is a drug which dramatically improves the survival of hES

5733 | Nov 05 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

MK 8776 is a potent and functionally selective targeting cell

2848 | Oct 30 2013

SCH 900776 is not a potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. [Read the Full Post]

PHA848125 is a spectrum selective multi kinase inhibitor of cyclin dependent kinases

2627 | Sep 17 2013

PHA-848125 is a potent, ATP-competitive CDK inhibitor for CDK2 with IC50 of 45 nM. It is >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7. Phase 2. [Read the Full Post]

Y27632 is a selective inhibitor of the Rhoassociated kinase p160ROCK

5564 | Sep 12 2013

Y27632 2HCl inhibits ROCK-II while displaying little activity against PKC, cAMP-dependent protein kinase and myosin light-chain kinase (MLCK) with Ki of 26 μM, 25 μM and > 250 μM, respectively, as well as PKA activated by another Rho-family GTPase member, Cdc42. [Read the Full Post]

STA9090 is a novel synthetic small molecule inhibitor of heat shock protein 90

2625 | Aug 31 2013

Ganetespib is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. [Read the Full Post]

Roscovitine is an experimental drug candidate

2896 | Aug 12 2013

Saracatinib also potently inhibits other Src tyrosine kinase family members including c-Yes, Fyn, Lyn, Blk, Fgr, and Lck with IC50 from 4-10 nM. Saracatinib sensitively inhibits Src Y530F NIH 3T3 with IC50 of 80 nM. [Read the Full Post]

PHA767491 is a newly discovered type of antitumor drugs

2604 | Jul 23 2013

PHA-767491 displays approximately 20-fold selectivity for Cdk1, Cdk2 and GSK3-β, 50-fold selectivity for MK2 and Cdk5 and 100-fold selectivity for PLK1 and CHK2. [Read the Full Post]

SCH 900776 is targeting cell cycle checkpoint kinase

3279 | Jun 08 2013

SCH 900776 is not a potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. SCH 900776 shows no significant inhibition of cytochrome P450 human liver microsomal isoforms 1A2, 2C9, 2C19, 2D6, and 3A4. [Read the Full Post]

y27632 is a biochemical tool used in the study of the rho associated protein kinase signaling pathways

5908 | Jun 07 2013

Oral administration of Y-27632 2HCl at 30 mg/kg significantly decreases the blood pressure in a dose-dependent manner in spontaneous hypertensive rats, renal hypertensive rats, as well as deoxycorticosterone acetate (DOCA)-salt hypertensive rats. [Read the Full Post]

Taxol is a mitotic inhibitor used in cancer chemotherapy

2844 | May 06 2013

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel. [Read the Full Post]

Olaparib for the treatment of the BRCA1 or BRCA2 gene mutations in cancer

3440 | Jan 23 2013

A broad range of pathological disorders is linked to oxidative stress, including carcinogenesis and several age-dependent disorders . Oxidative stress is defined as an imbalance Olaparib in which the production of reactive oxygen species overcomes the antioxidative cell defence system [Read the Full Post]

Alvocidib is a cyclin dependent kinase inhibitor under clinical development for the treatment

1827 | Jan 17 2013

Alvocidib is also considered a major pathogenic factor. Lipid A, also referred to as endotoxin, is the hydrophobic membrane anchor of LPS and is known to be a potent inducer of the host innate immune system [Read the Full Post]

ROCK Kinase is involved in cytokinesis

5920 | Dec 03 2012

The first evidence that the JNK pathway, the low level of expression in SMC Lon RGS4 ch Lt, then led end F F promotion from SMC contraction. Inhibition of tonic RGS4 expression by JNK pathway represents a novel mechanism for the contribution of the JNK pathway in the regulation of smooth muscle contraction. crosstalk between MAPK and JNK by other means NFkB not well ROCK Kinase understood. [Read the Full Post]

Dinaciclib is supported by several previous studies

2534 | Nov 30 2012

The first evidence that the JNK pathway, the low level of expression in SMC Lon RGS4 ch Lt, then led end F F promotion from SMC contraction. Inhibition of tonic RGS4 expression by JNK pathway represents a novel mechanism for the Dinaciclib contribution of the JNK pathway in the regulation of smooth muscle contraction [Read the Full Post]

CANCER AND CDK INHIBITION

3477 | Sep 16 2012

CDK/CYCLIN DEPENDENT KINASES: Among a large number of cell cycle regulators, cyclin dependent kinases also known as CDKs are known to be very important ones. These kinases play a crucial role in the processes of transcription, mRNA processing and cellular differentiation. These kinases have a small structure with an important kinase domain and depend on another small protein for proper activity i.e., cyclin. As these are very important kinases in cell cycle, they can be targeted in order to prevent proliferation of cancer cells. Inhibition of these kinases has shown induction of apoptosis especially in cancer cells. Various inhibitors have been designed against different kinases to fight cancer and inflammation, preserved in kinase inhibitor library for screening amongst these CDK2 inhibitors have been found to be most effective. Inhibiting cell cycle regulators may have some hazards as well; therefore inhibitors should be developed carefully in order to avoid these side effects. [Read the Full Post]

ONCOGENES AND HSP90 INHIBITORS

5247 | Aug 24 2012

PATHWAY OF HSP90 AND CANCER CELL LINES: Heat shock protein 90 or Hsp90 is actually a non-fibrous protein which gained its name from its molecular weight that is 90kDa. Hsp90 is most abundant cytoplasmic protein which plays a significant role in cells by acting like a molecular chaperone for many proteins related to some important signaling cascades of the cell. Different proteins chaperones that are existing in the cell, involve serine/theronine kinases and tyrosine kinases as well hence they are very much important for the proper regulation of cell growth and cell cycle. A detailed research is carried out to describe the relation between Hsp90 and cancers. To inhibit this chaperone i.e. Hsp90, the simple strategy of designing Hsp protein inhibitor was developed when Hsp90 was found to be existing in different cancerous cell lines activated through the activation of oncogenes. It has been proved a very fruitful therapy for cancer. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

5538 | Aug 16 2012

HSP90 CASCADE AND CANCER CELLS: Hsp90 or the Heat shock protein 90 is a non fibrous protein that gained its name on the basis of its molecular weight i.e., 90kDa. Heat shock protein 90 is the most abundant protein present in cytoplasm that plays a significant role in the cells by acting as molecular chaperones for different proteins associated with some important signaling pathways in the cells. Various molecular chaperones existing in the cells, involves in the tyrosine kinases and serine/theronine kinases as well, so they are very important for proper regulation of cell cycle and cell growth. A complete research has been done to describe the relation between cancer and Hsp90. For the inhibition of Hsp90 chaperone a simple strategy is designed i.e., development of Hsp-60 inhibitor in case of presence of Hsp90 in the cancerous cells and activated by the activation of various oncogenes. It was proved to be an efficient therapy for the treatment of cancer. [Read the Full Post]

CANCER INHIBITION BY CDK

3303 | Aug 09 2012

CYCLIN DEPENDENT KINASES OR CDK: Cyclin dependent kinases or CDKs are also found to be very famous ones among the long list of regulators of cell cycle. These kinase enzymes play a very crucial role in various processes like mRNA processing, cellular differentiation and, transcription. These kinase enzymes have a very important kinase domain and a small structure and they also depend upon another protein i.e cyclin for their proper activity. To stop the proliferation of cancer or tumor cells these kinases can be targeted as they are an important part of cell cycle. By the inhibition of these kinase enzymes apoptosis is induced in the cells especially the tumor cells. Different kinase inhibitors have been designed to fight against these kinases and stop the inflammation, conserved in the kinase inhibitor library and amongst these inhibitors, CDK inhibitors were found to be very effective ones. The inhibition of the regulators of cell cycle may also cause some hazards; so the inhibitors should be designed very carefully and efficiently in order to avoid the side effects. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

5343 | Aug 02 2012

HSP90 PATHWAY AND CANCER CELLS: Heat shock protein 90 or Hsp90 is a non-fibrous protein that has gained its name from its 90kDa molecular weight. This is the most abundant protein present in cytoplasm and plays an important role in the cell by acting as a chaperone for many of the proteins involved in important signaling pathways of the cell. There are various proteins chaperones which are present in the cell, includes TKs or tyrosine kinases and theronine/serine kinases as well and these are very important for the regulation of cell cycle and growth. Detailed research has been conducted to connect cancers and Hsp90. As Hsp90 has shown by different cancerous cells which are activated via activating oncogenes a simple strategy for the inhibition of this chaperone has developed by designing Hsp90 inhibitors. This approach has been fruitful for cancer therapy. [Read the Full Post]

CDK INHIBITOR AND CELL CYCLE

3073 | Jul 27 2012

CYCLIN DEPENDENT KINASES OR CDKs: Cyclin dependent kinases are amongst one of the most vital kinase enzymes in the regulation of cell cycle. These are also abbreviated as CDKs and due to a crucial role these enzymes are implicated in transcription, nerve cells differentiation, and mRNA processing. These enzymes have small structure but having an important part that is kinase domain. It is reported that the inhibition of CDK leads to the apoptosis of cells specifically in case of cancer cells, so it is important in controlling the cell cycle. Uncontrolled cellular proliferation can lead to the cell cycle aberrations. Various compounds found in kinase inhibitor library have shown activity against inflammations and cancer and among these inhibitors CDK inhibitors are most effective against CDKs. The development of inhibitors has to be performed carefully as there may be some of the other potential hazards of cell cycle dysregulation and some other effects as well. [Read the Full Post]

PACLITAXEL – A MICROTUBULE INHIBITOR WITH MULTIPLE ROLES

3153 | Apr 04 2012

PACLITAXEL: Paclitaxel is an inhibitor of mitosis and it was discovered in the bark of a tree called Taxus brevifolia and later on its presence was also reported in hazel cells. Many of the cancer drugs target microtubules in the cancer cells, Paclitaxel microtubules inhibitor is a new hope for cancer treatment. The structure of this compound is complex as it contains diterpene along with an oxatane ring and taxane. The generic name has been changed by the manufacturers of Paclitaxel that was Taxol the brand name of this inhibitor is Abraxane and any one can buy Paclitaxel for medicinal usage. Paclitaxel is soluble in methanol and DMSO and in order to gain long term stability for this compound one should keep it away from any strong acidic or alkaline solution. The Paclitxel price is variable as it depends on its purity and Paclitaxel supplier. Its cost is reasonable and one can purchase Paclitaxel for research purposes as well. [Read the Full Post]

PACLITAXEL – MULTIPLE ROLES AS MICROTUBULE STABILIZER

3472 | Mar 19 2012

Introduction: Mitosis and Cytokinesis An essential part of the cell cycle is the M phase where the cell physically divides into two unique cells. This process is consists of two different phases mitosis and cytokinesis. Cytokinesis is the phase where the contents of the cell are divided into two equal portions along with the duplicate chromosomes and nuclei. The cell membrane then pinches together and eventually splits into two segments. Mitosis, on the other hand is the division of the duplicate chromosomes and nuclei into opposite ends of the cell. To do this; microtubule form from one end of the elongated cell to the newly formed chromosomes, these tubules then decrease in length pulling the chromosomes pairs apart. The same happens for the nuclei. This process is complex and involved but it is sufficient to indicate that action of inhibitors against the dismantling of the microtubules would halt the cell separation causing apoptosis to initiate. A small molecule that can induce such a reaction is Paclitaxel microtubule stabilization has been used as the standard treatment for a variety of cancer types for many years. [Read the Full Post]

HSP INHIBITORS AGAINST PROTEIN FOLDING

4505 | Mar 19 2012

Introduction: Cellular Quality Assurance The network of chemical reactions linked to the mechanisms behind cellular growth, proliferation and differentiation are complex. Referred to as biochemical pathways these mechanisms operate on some simple principles starting with the receipt of a message from the host system to the cell itself. The pathway system can be likened to a production line facility with the product being a normal health cell. So mechanisms exists for stock piling of raw materials, for the synthesis of component parts, for the recycling of waste materials, for the removal of unwelcome molecules, quality assurance and final product viability. One the key aspects of cellular growth is the delicacy of the whole process, it does not take much to drive a mechanism off balance and produce a faulty product, to ensure quality under stress induced conditions a series of proteins exist referred to as Heat Shock Proteins that assess the quality of proteins being constructed for cell growth purposes. [Read the Full Post]

CDK INHIBITORS IN REGULATING CELL CYCLE

2575 | Mar 20 2012

Introduction: Cyclin dependent Kinases In total 512 human versions serine/therione/tyrosine kinases have been discovered leading to the theoretical formation of multiple pathways that govern all aspects of cellular life and death. Research has confirmed many of these controls but aspects of these mechanisms still remain controversial. One of earliest kinase pathways to be discovered was the Cyclin dependant kinases. These kinases were shown to be a major regulatory mechanism of the cell cycle growth patterns, apoptotic processes, pain, gene transcription, and RNA formation. Mechanisms with which CDK action and response is controlled can be by phosphorylation or degradation, natural inhibitory proteins, movement of the kinase around the cell or nucleus and by formation complexes with other regulatory proteins. [Read the Full Post]

ROSCOVITINE – A CONTROLLER OF THE CYCLINS

1930 | Mar 20 2012

CDKs AND CANCER: In cellular regulation which is one of the important processes, different enzymes are important and among these cyclin dependent kinases or CDKs play vital role. Mostly cancers are linked with malfunctioning of these CDKs. There are two forms of these malfunctioning, one is the over expression of the CDKs gene and second is about the regulatory proteins of CDKs which may be absent or abnormal. In the field of cancer treatment various inhibitor have been developed which inhibit the function of different vital enzymes. In case of CDKs the development of the unique compound to inhibit the activity of abnormal enzymatic activity is not as simple because the activity of different CDKs is time specific in the cell cycle, therefore a molecule should be well timed up with CDKs. A good number of CDK inhibitors are developed and are mostly in clinical trials phases among those Roscovitine CDK inhibitor is active inhibitor. [Read the Full Post]

THIAZOVIVIN: THE PLURIPOTENCY INDUCER

4828 | Mar 20 2012

POTENTIAL OF EMBRYONIC STEM CELLS OF HUMAN (hESCs): The stem cells are not only known for their property of pluripotency in nature which means they have the potency to replicate in an indefinite manner but also famous for their capability of getting differentiate into all other kinds of cells and organelles from the three basic germinal layers named as ectoderm, mesoderm and endoderm. Embryonic stem cells of human (hESCs) have the ability of producing various numbers of types of cells in contrast to adult stem cells having the capability of producing only a limited cell types. Due to their pluripotency hESCs or human embryonic stem cells are of great interest and importance for the scientists and researchers as they are being used for detection and analysis of different genetic disorders of human in their research. The successful models of Human Embryonic Stem Cells are made for Fragile-X syndrome and Cystic fibrosis (CF) etc like genetic maladies and their will be many more in upcoming years. In olden years the usual practice was to use embryo to generate pluripotent stem cells which is brought down very significantly due to the process of insertion of various genes like Sox2, Oct4 and Klf4 etc into differentiated cells. These genes can enhance the pluripotency in differentiated cells and make them exactly like embryonic stem cells. A recent more advanced approach is to use molecules like Thiazovivin. [Read the Full Post]

TAXOL: BEFORE AND NOW

2859 | Mar 18 2012

Inhibition of cell division A well know cellular function is that of mitosis; which is the biological function whereby a cells nucleus splits into two identical units. The process is accompanied by cytokinesis where the cell membrane, cytosole and separate nuclei divide into to cells. This complete process is referred to as the”M” phase in the cell cycle theory. The complete process is supported by a scaffolding type structure called microtubules which provide the framework for cytokinesis and mitosi. A mitotic inhibitor is one which interferes with the stability of the microtubules which is of relevance in chemotherapy since unregulated cell division is one the strongest difference between tumor and normal cells. This difference can be exploited by a specifically designed inhibitor. Taxol, more commonly called Paclitaxel, is an inhibitor which disrupts the dismantling of the microtubules during cell division, hence cell mitosis cannot occur. Taxol is standard therapy in many forms of cancer including sarcoma, breast cancer, NSCLC, SCLC, ovarian cancer as well as head and neck cancer. [Read the Full Post]

CDK INHIBITOR AGAINST CELL CYCLE DYSREGULATION

2084 | Mar 19 2012

The cell Cycle One of the most important discoveries of the 20th century was the revelations of how cells were governed and regulated in their growth patterns. This process was described in a cell cycle pathway along with regulatory mechanism and quality control functions. Each individual cell is capable of replicating itself but is not always in the processes of doing so. This resting state is referred to as the G0 phase. An extracellular signal is sent to the cell via the cell surface receptors that trigger the cell to enter the G1 phase. This is the first step in cell replication and the cell gathers nutrients as well as protein building blocks from the systemic circulation, this allows the cell to increases in size. Control proteins regulate the amount of material gathered by the cell and the size to which in grows. If certain specifications are met the cell moves from the G1 phase to the S phase of the process. [Read the Full Post]

PD 0332991 – THE POTENT CDK INHIBITOR

3211 | Mar 19 2012

PD 0332991 PROPERTIES: One of the most important functions any cell can do is the reproduction of itself, identical down to the finest degree. The process that achieves the basic necessity of life itself is called the cell cycle and is a highly controlled / regulated process. This process is divided into two stages; the first is the interphase stage which has four distinct phases. The second stage is the cell division stage and this consists solely of the cell mitosis. Starting at stage 1 the cell is usually at rest or in a condition where no replication is occurring, this is referred to as the G0 phase. When a cell receives an external trigger to divide the cell moves into the G1 phase, here the cell will accumulated nutrients and molecules necessary for the construction of all the components of a new cell. Cells use this material to increase in size to accommodate the new material and to generate sufficient cell membrane so a division can occur. The G1 phase has control mechanisms to recognize the successful completion of all necessary components of this phase. [Read the Full Post]

AZD1152 – AN AURORA KINASE INHIBITOR

6017 | Mar 13 2012

Inhibition of AURORA KINASES in relation to cancer: Mitosis is a key process in the regeneration of cellular material and two key regulators of this function are serine and threonine kinases which are more commonly known as Aurora Kinases. Three isoforms of the aurora kinase have been isolated in human tissue (A,B and C) which function on different aspects of the mitosis cycle. Aurora kinases are significant as targets for chemotherapeutic action since they are elevated in many different cancer types. Small molecule inhibitors of aurora kinases, such as VX-680 (Tozasertib), ZM447439 and Hesperadin, have been developed and successfully trialed on several cancer groups including breast, colon, prostate and in acute myeloid leukemia (AML). [Read the Full Post]

ROSCOVITINE – CONTROLLING THE CYCLINS

3252 | Mar 13 2012

Introduction: Cyclin-dependant kinase Inhibitors: Another family of proteins that are involved in the regulation of cellular growth are the cyclin dependant kinases (CDK’s). These enzymes are known to be involved in the regulation of the cell cycle (Mitosis (M phase) – Gap phase (G1) – Synthesis (S) – Gap phase (G2)) as well as regulating transcription, mRNA and differentiation of nerve cells. CDK’s contain not much more than a kinase domain and are serine / threonine phosphorylators. The substrate for CDK’s is a regulatory protein called cyclin of which 12 are known. The activity of CDK’s is restricted to the CDK – complex which in human cells there are at least 9 known variations. Different CDK-complexes are involved at different stages of the cell cycle process each one controlling one or more factors. In current theory CDK’s are the diving motivation behind each phase of the cell cycle and deviations in the CDK activity from the normal can cause unregulated proliferation or simple a tumor. Hence direct targeting of the aberrant CDK activity would ideally be a therapeutic possibility. However, with CDK activity essential for all cell cycle processes there was no theoretical distinction between tumor and normal cells hence significant toxicology could be expected. Recently new research changed this theory; it indicated that tumor cell cycle was controlled by an interphase CDK that was specific to the tumor cell. With this inhibitors of CDK activity could now be implemented against tumor growth patterns. For this purpose smaal molecule inhibitors were designed, of which the Roscovitine CDK inhibitor is one of several being tested in certain tumor types. [Read the Full Post]

TOZASERTIB IN CLINICS FOR AURORA INHIBITION

5509 | Mar 13 2012

AURORA KINASE INHIBITION AND TOZASERTIB:  Three isoforms of the aurora kinase have been isolated in human tissue (A,B and C) which function on different aspects of the mitosis cycle. Aurora kinases are significant as targets for chemotherapeutic action since they are elevated in many different cancer types. Small molecule inhibitors of aurora kinases, such as VX-680 (Tozasertib), ZM447439 and Hesperadin have been developed and successfully trialed on several cancer groups including breast, colon, prostate and in acute myeloid leukemia (AML). The initial results obtained for the Tozasertib Aurora kinase inhibitor has lead to its advancement into phase 1 and phase 2 clinical trials. [Read the Full Post]

The combination of VE-465 and vincristine, the potential therapy for leukemia

7776 | Oct 25 2011

Leukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of white blood cells, and studies on the treatment of the disease have been carried out for many years. At present, a variety of small-molecule agents targeting specific leukemogenetic molecules have been used in preclinical or clinical treatment of leukemia. For example, BCR/ABL kinase inhibitors, including imatinib, nilotinib and dasatinib have shown the effective treatment against BCR/ABL-positive leukemia. However, novel agents and therapy may be still needed, since monotherapy shows only limited clinical efficacy. [Read the Full Post]

Roles of Hsp90 in wound healing and cancer

5772 | Oct 24 2011

Wound healing is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. At present, local growth factors are considered to be the driving force for wound healing and only recombinant human platelet-derived growth factor-BB (PDGF-BB) has been approved by US FDA for topical treatment of diabetic ulcers. However, the use of PDGF-BB in clinical trials has been limited for its modest efficacy, high cost and risk of causing cancer. Thus, novel treatment for wound healing is needed to be explored. [Read the Full Post]

Novel CDK2 Inhibitors as Anti-Tumor Agents

2781 | Sep 09 2011

Conventional anti-cancer drugs have mainly focused on targeting DNA synthesis and cell division.n order to avoid these adverse effects, investigators begin to develop a new class of anti-cancer agents, and signal transduction or secondary message inhibitors is one of the successful research findings. [Read the Full Post]

Takayuki Ikezoe (2008). “Aurora kinases as an anti-cancer target” Cancer Letters 262(2-3): 1–9

4510 | Jun 13 2011

This review highlights the function of Aurora kinases in the regulation of mitosis and presents the rationale for these kinases as an anti-cancer target. I also review recently developed inhibitors of Aurora kinases. [Read the Full Post]

Narumiya, S., M. Tanji, et al. (2009). "Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion." Cancer Metastasis Rev 28(1-2): 65-76.

5726 | Jun 7 2011

This review summaries the Rho signaling in transformation, metastasis and invasion. It explains the relationship between Rho signaling and tumor cells, and it gives the perspectives in this review. [Read the Full Post]

Sarli, V. and A. Giannis (2008). "Targeting the kinesin spindle protein: basic principles and clinical implications." Clin Cancer Res 14(23): 7583-7587.

3999 | Jun 2 2011

This review describles the function of the kinesin spindle protein. This article also summary the inhibitors of the kinesin spindle protein. [Read the Full Post]

Peters, J. M. (2006). "The anaphase promoting complex/cyclosome: a machine designed to destroy." Nat Rev Mol Cell Biol 7(9): 644-656.

3758 | May 8 2011

This article which was published in Nature review molecular cell biology reviews not only APC/C subunits and substrates, but the functions, regulation, and inhibition of APC during the 10 years since APC was discovered. [Read the Full Post]

Barr, F. A., H. H. Sillje, et al. (2004). "Polo-like kinases and the orchestration of cell division." Nat Rev Mol Cell Biol 5(6): 429-440

3429 | Apr 22 2011

This review introduces the Plk structure and regulation, Plk function at the G2/M transition, in cytokinesis, and chromosome segregation, and the interaction between PLKs and other targets. [Read the Full Post]

Chiosis, G., M. Vilenchik, et al. (2004). "Hsp90: the vulnerable chaperone." Drug Discov Today 9(20): 881-888.

4405 | Apr 19 2011

Agents that interact with its C-terminus or modify its post-translational status represent additional ways of interfering with chaperone activity. This review will discuss several emerging classes of Hsp90 inhibitors and their modes of action. [Read the Full Post]

Riento, K. and A. J. Ridley (2003). "Rocks: multifunctional kinases in cell behaviour." Nat Rev Mol Cell Biol 4(6): 446-456.

4944 | Mar 3 2011

This article introduces regulation of ROCK activity, ROCK function and ROCK inhibitors. This review concludes knowledge of ROCK in different ways. [Read the Full Post]