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ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Blog of Signaling Pathways

Lonafarnib synergizes with azoles against Aspergillus spp. and Exophiala spp

426 views | Jun 13 2019

Qiao J et al. demonstrated that lonafarnib could enhance the in vitro antifungal activity of itraconazole, posaconazole and voriconazole against Aspergillus spp. and E. dermatitidis, suggesting that azoles, especially itraconazole and posaconazole, combined with farnesyltransferase inhibitor might provide a potential strategy to the management of Aspergillus and Exophiala infections. However, further studies are warranted to elucidate the underlying mechanism and to investigate the potential of reliable and safe application in clinical practice. [Read the Full Post]

Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase

908 views | Jun 12 2019

Huang WS et al. showed that brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial. [Read the Full Post]

Trametinib Induces Neurofibroma Shrinkage and Enables Surgery

504 views | Jun 11 2019

Vaassen P et al. suggested that MEK inhibitors are likely to play a significant role in providing a cure for one of the most devastating manifestations of NF1. [Read the Full Post]

Combination of Emricasan with Ponatinib Synergistically Reduces Ischemia/Reperfusion Injury in Rat Brain Through Simultaneous Prevention of Apoptosis and Necroptosis

568 views | Jun 10 2019

Tian J et al. concluded that combination of emricasan with ponatinib could synergistically reduce I/R injury in rat brain through simultaneous prevention of apoptosis and necroptosis. Our findings might lay a basis on extension of the clinical indications for emricasan and ponatinib in treating ischemic stroke. [Read the Full Post]

Effect of CHK1 Inhibition on CPX-351 Cytotoxicity in vitro and ex vivo

415 views | 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 views | 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]

Effect of bucladesine, pentoxifylline, and H-89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain

525 views | Jun 09 2019

Salehi F et al. indicated PTX, H-89, and Db-cAMP affect the thermal-induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide-dependent protein kinases. [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 views | 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]

NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors

814 views | Jun 08 2019

Park HR et al. suggested that combinational treatment with NK cell-based immunotherapy and cetuximab may be promising for patients with TKI-resistant NSCLC. [Read the Full Post]

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

731 views | Jun 08 2019

Lehmann C et al provided functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies. [Read the Full Post]

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

750 views | Jun 07 2019

Stone RM et al. indicated the addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. [Read the Full Post]

Regulation of cisplatin-resistant head and neck squamous cell carcinoma by the SRC/ETS-1 signaling pathway

469 views | Jun 06 2019

Yang Z et al. demonstrated that the SRC/ETS-1 pathway plays a crucial role and could be a key therapeutic target in cisplatin-resistant HNSCC treatment. [Read the Full Post]

Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin

734 views | Jun 06 2019

Wang Q et al. suggested that elevating H3K27me3 level can improve drug sensitivity in CRC patients. [Read the Full Post]

Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation

563 views | Jun 05 2019

Horbelt D et al. suggested these inhibitors as suitable tools to promote functional myogenesis. [Read the Full Post]

Differential effects of p38 MAP kinase inhibitors SB203580 and SB202190 on growth and migration of human MDA-MB-231 cancer cell line

416 views | Jun 05 2019

Düzgün ŞA et al. indicated the ERK1/2 phosphorylation level was not modified by low concentrations (1 or 5 µM) of SB202190 and SB203580; while a high concentration (50 µM) of both inhibitors caused significant reductions in the ERK1/2 phosphorylation. In addition, it was determined that both p38 MAPK inhibitors caused significant increases on the Ser15 phosphorylation of mutant p53 in MDA-MB-231 under these experimental conditions; while SB202190 was more potent than SB203580. [Read the Full Post]

The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development

735 views | Jun 04 2019

Xing T et al. indicated that PDPK-1 and other intrinsic kinases downstream of IGF-1 are key regulators of rod photoreceptor formation. [Read the Full Post]

Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580

436 views | Jun 04 2019

Conway JG et al. showed that GW2580's selective inhibition of monocyte growth and bone degradation is consistent with cFMS kinase inhibition. The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes. [Read the Full Post]

Inhibitory Activities of Blasticidin S Derivatives on Aflatoxin Production by Aspergillus Flavus

527 views | 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]

Regulation of Skeletal Muscle DRP-1 and FIS-1 Protein Expression by IL-6 Signaling

764 views | Jun 03 2019

Fix DK et al. elevated IL-6 can directly induce DRP-1 and FIS-1 expression through gp130 signaling in cultured myotubes and skeletal muscle. Furthermore, ERK 1/2 signaling is necessary for the IL-6 induction of DRP-1 and FIS-1 expression in myotubes. [Read the Full Post]

ASP2215 in the treatment of relapsed/refractory acute myeloid leukemia with FLT3 mutation: background and design of the ADMIRAL trial

1033 views | Jun 02 2019

Gorcea CM et al. showed that ASP2215 (gilteritinib) is a novel, dual FLT3/AXL inhibitor with promising early phase trial data (NCT02014558). [Read the Full Post]