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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

HDAC INHIBITORS AGAINST CANCERS

4520 views | Aug 01 2012

EPIGENETIC MODULATION VIA HDAC INHIBITION: Histones acetylation is vital process in the functions like cellular growth and cell death by inhibiting the transcription of proteins which is caused by the removal of acetyl groups from histones as a result the DNA binding increases and DNA is condensed. When this process is disturbed it leads to uncontrolled growth of cells leading to the formation of cancers and also neurodegenerative diseases. HDAC inhibition for the treatment of cancer comes by the use of HDAC inhibitors. Successful studies elucidating mechanisms of HDAC inhibitors led to their vast applications in different clinical and preclinical studies. HDAC levels can be assessed by using various assays developed for this purpose. These assays can be performed in lab by the help of kits. Researchers can perform microplate reader compatible and nonisotopic HDAC inhibitor assay and one for compound profiling and robotic screening and in addition to this simply a flourogenic assay can be performed for high-throughput screening. [Read the Full Post]

RALTEGRAVIR- AN INTEGRASE INHIBITOR

3654 views | Jul 30 2012

HIV-I AND INTEGRASE HIV one of the most tricky viruses on earth that cause immunodeficiency in humans is being studied allot. It is responsible for a deathly disease known AIDS which is a focus of attention of many researchers since last decades. Due to its wide spread and occurrence throughout the world has compelled the scientists to look for a drug that may effectively cure the disease. HIV contains different types of enzymes and genes that help it to utilize the genes and proteins of its host. The most important among all is the integrase enzyme that helps it in integration of its genome into that of the host. Integrase has been an attractive target for the devising a therapy against the disease. A lot of research is being done on integrase inhibitors and several integrase inhibitors have been discovered by high throughput screening that prevent the integration of genome of virus into that of the host hence preventing the proliferation of the host cell. These inhibitors have shown efficacious results when used against HIV-I. One of the examples of such inhibitors is Raltegravir integrase inhibitor. This drug is first of such inhibitors to get FDA approval and is a blessing for the patients of HIV. [Read the Full Post]

mTOR INHIBITORS AND CANCER THERAPY

3351 views | Jul 31 2012

mTOR SIGNALING PATHWAY: FRAP1 or FK506-binding protein 12 - rapamycin associated protein-1 is another name of mTOR (mammalian target of rapamycin) which is a serine/threonine protein kinase and encoded by FRAP1gene in human genome. Many of the cellular processes are reported to be controlled by mTOR which is in response to nutrient and energy status, these processes includes cell proliferation, cell growth, transcriptional regulation migration of proteins and cell survival. Therefore a straight forward approach is to design mTOR inhibitors that would control the process of mTOR by inhibiting its actions in the cancer cells where normal processes are aberrant. mTOR signaling pathway can be checked by these inhibitors leading to control of tumor and cell growth or limiting tumorigenesis. [Read the Full Post]

EGFR INHIBITORS AGAINST TUMORS

4736 views | Jul 29 2012

EGFR INHIBITION: There are few pathways which play important roles in the cellular functioning and among these EGFR (epidermal growth factor receptor) pathway is one which is vital for the cell growth, proliferation and survival. The significance of this pathway can only be understood by the formation of cancers and fatal diseases associated with uncontrolled growth of cells due to dysregulation of EGFR signaling pathway. Mutated or over expression of EGFR is linked with many types of cancers for example breast, colon and lung cancers and also with glioblastoma multiform, epithelial and anal cancers. Therefore an attractive strategy to treat cancers was EGFR inhibition by using EGFR inhibitors. In addition to this use in clinics these are also involved in patient survival and various EGFR agonists and antagonists are also being used for the elucidation of different other pathways and effects of EGFR signaling pathway on them. These inhibitors are available at normal prices from any of the relevant supplier. [Read the Full Post]

CDK INHIBITOR AND CELL CYCLE

3073 views | 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]

NILOTINIB AND PHILADELPHIA

6344 views | Jul 25 2012

CML AND PHILADELPHIA CHROMOSOME During meiosis the fusion of two genes including BCR a breakpoint cluster and ABL tyrosine kinase results in the formation of Philadelphia chromosome. The resultant fusion protein expressed due to Philadelphia chromosome is not controlled and function abnormally leading to an oncoprotein. Chronic myelogenous leukemia or CML is caused by this fusion oncoprotein in 90% of the patients of CML. Due to huge part of this protein in CML, in drug development for cancer treatment this protein is being targeted by researchers by the help of small molecule screening. Nilotinib AMN-107 is one of the inhibitor used for this purpose to cure CML. [Read the Full Post]

c-MET INHIBITORS IN CANCER TREATMENT

3155 views | Jul 26 2012

APPLICATION OF c-MET INHIBITION IN CANCERS: c-Met is a proto-oncogene which encodes HGF-R or hepatocyte growth factor receptor, hyperactivation of this gene activates certain changes such as formation of new blood vessels or angiogenesis which leads to invasive tumor growth. Met aberrant regulation reported to be a cause of many cancers such as stomach cancer, liver cancer, ovarian cancer, breast cancer, brain and thyroid cancers. Due to this characteristic of c-Met gene inhibition has become an attractive approach for therapeutic use. Therefore a huge research is being done for the development of c-Met antagonists or c-Met inhibitors which have therapeutic or clinical implications. In addition to this application c-Met antagonists or agonists are also being utilized for the understanding of various cellular pathways and imparting light on the interaction of other molecules with c-Met. Commercially many of these like kinase inhibitors are available from any of the suppliers and one can easily access to them. [Read the Full Post]

AKT INHIBITORS AS ANTI TUMOR AGENTS

4392 views | Jul 24 2012

AKT PATHWAY AND CANCERS: AKT is a kinase specific for threonine/serine amino acids which is also known as Protein kinase kinase B (PKB). This kinase is involved in various cellular pathways such as glucose metabolism, apoptosis, transcription and the most important functions are cell migration and proliferation. In cancer cells many of the crucial functions are controlled by AKT which depicts its importance. AKT is downstream to PI3K and mostly it is hyper activated during formations of cancers therefore taking a part in tumorigenesis through a hyperactive PI3K/AKT/mTOR pathway. As mutations, translocations and amplifications in PI3K/AKT/mTOR pathway result into hyperactivation of this pathway are more frequent than other signaling pathways. AKT inhibitors are one of the most feasible approaches to fight against cancer. [Read the Full Post]

PARP INHIBITOR: A MULTI PURPOSE AGENT

3865 views | Jul 23 2012

PARP INHIBITOR AND ITS APPLICATIONS: Poly ADP-ribose polymerases or PARP are translated by the PARP genes which are a part of human genome. PARP are vital proteins for some of the most important functions such as DNA repair mechanism and apoptosis. There are many reports of research in which a close relation of PARP inhibition is noted with BRCA1 and BRCA2 which are associated with onset of ovarian and breast cancer. Based on these research reports PARP inhibition has become a novel tool for the treatment of different types of cancers and tumors. PARP inhibitors have shown efficient results against BRCA genes. PARP protein inhibitor has unique property of not affecting normal cell; therefore these inhibitors are specific for cancer cells. The choice for cancer treatment with least side effects is becoming famous due to PARP inhibitors which are potent anti cancer agents. [Read the Full Post]

RAPAMYCIN-A BROAD SPECTRUM DRUG

3267 views | Jul 22 2012

RAPAMYCIN- INHIBITS mTOR In all around the world the treatment of cancer is a hot topic of research and as a result of extensive work in this field many of the novel therapeutic agents are undergoing clinical trials in order to sort out drugs with least side effects. In research and development efficacy is not the only thing which is under considerations but also the specificity. In cancer treatment the drugs are mostly designed as regulatory or inhibitory agents for cell cycle proteins. Rapamycin 53123-88-9 is one such inhibitor which targets mTOR protein kinase enzyme. Checking the functions of mTOR proteins cellular growth and proliferation can be controlled by affecting transcription and translation of specific genes. Rapamycin mTOR inhibitor is being used since decades for the treatment of cancer. One of the effective results has been reported for cancer cure and some other disorders are also noted to be treated by this drug. Four decades back this inhibitor was discovered as an anti-fungal drug. Rapamycin is also used for transplantation cases where it acts as an immunosuppressing compound as it also inhibits cell cycle process. One of the major usages of this compound is its application for HIV treatment. [Read the Full Post]

PAZOPANIB: INTRODUCTION

4324 views | Jul 19 2012

PAZOPANIB: INTRODUCTION One of the very important anti-tumor drugs Pazopanib VEGFR inhibitor also known as Pazopanib Votrient is being produced by the very popular pharmaceutical company which is GlaxoSmithKline. It is selling this drug with commercial name of Votrient. Pazopanib inhibits the angiogenesis by blocking VEGF R1, R2 and R3 with their β subtypes and also inhibits c-kit RTKs as well as PDGFR-a. Though Pazopanib is tiny molecule yet it gains popularity due to its extensive potential on various kinds of malignancies. Pazopanib VEGFR-PDGFR inhibitor has now been approved to enter the clinical trials. It was revealed by the Pazopanib structure that it contained a sulfonamide group. It is marketed in 25mg of packaging with Pazopanib price of approximately $100 as Votrient or GW786034 and anyone can purchase Pazopanib for research or experimental purposes from supplier Pazopanib. Prices are being varied from supplier to supplier. Pazopanib solubility revealed it is best soluble in DMSO while it is absolutely insoluble in water and ethanol. Storing at -20oC shows stability for approximately 2 years. [Read the Full Post]

HIGH THROUGHPUT SCREENING IN DRUG DISCOVERIES

3645 views | Jul 18 2012

HIgh throughput screening: For the treatment of life taking diseases such as cancers are always in a need to be treated with novel therapeutics, in order to full fill this task many techniques are accepted. High throughput screening is found as the most remarkable strategy in order to discover new potent drugs. Another name of this technique is High throughput screening assay and this technique is being developed more and more due to latest automatic machines which also ensures its accuracy and speed. For a drug discovery High throughput screening works under pharmaceutical, biological or biochemical environment to find out the ability of drug against specific disease. Mostly the novel drug is based on the properties of any ligand, specific receptor, peptides enzymes or ion channels involved in a specific disease condition. This is a technique with dual benefits as there is another use of high throughput screening is the detection of various pathways which are potential for specific diseases. Screening libraries of kinases is one of the most important examples of high throughput screening as compared to old techniques. [Read the Full Post]

SUNITINIB-AN RTK INHIBITOR

3893 views | Jul 17 2012

SUNITINIB: INHIBITS MULTIPLE KINASES There are different cell signaling processes in metabolic resources which supervise other important cellular functions. One of the most vital types of cellular processes is tyrosine kinase pathways which control many other important pathways like cellular proliferation, growth, apoptosis and cell survival etc. When these tyrosine kinases are over expressed the abnormal cell growth has been noted, which is the reason of many lethal diseases such as cancer. The approach of designing inhibitors for tyrosine kinases is one of the leading fields in drug designing against cancers. It is possible that a single inhibitor can inhibit the functions of multiple tyrosine kinases. One of the examples of cancer associated with tyrosine kinase is breast cancer where VEGF pathway gets abnormal. Many carcinomas has been handled by using inhibitors of tyrosine kinases [2] and one example is gastrointestinal stromal cancer where such inhibitors are being used and one another example is ALL (acute Lymphoblastic Leukemia) treatment. [Read the Full Post]

TEMSIROLIMUS

3437 views | Jul 16 2012

TEMSIROLIMUS: INHIBITOR OF mTO RPATHWAY Protein kinase mTOR are the enzymes that come under the category of phosphatidylinositol 3-kinase or PI3-K that control the cell migration, cell multiplication, cell transcriptional and translational actions and cell survival. The fact that these inhibitors are involved in the above described processes, these enzymes have come into lime light for cancer therapy. In the recent years Temsirolimus mTOR inhibitor has got more popularity as compared to Rapamycin which was employed in the late years. For the cure of RCC or renal cell carcinoma Temsirolimus Torisel is among the rare inhibitors which is waiting for its approval by FDA. Temsirolimus 162635-04-3 is developed by a pharmaceutical company called Wyeth and it is administered to the patientsintravenously. [Read the Full Post]

PARP INHIBITOR: A THERAPEUTIC AGENT FOR ISCHEMIA, STROK AND CANCER

3876 views | Jul 15 2012

USES OF PARP INHIBITOR AND DOWNREGULATION OF PARP CASCADE Human genome consists of different genes one of which is PARP gene which translates to produce PARP or Poly ADP-ribose polymerases. Important functions of cells like programmed cell death and mechanism of DNA repair is being controlled by these proteins. Breaks in single strand of DNA are specifically repaired by these proteins. Since BRCA1 and BRCA2 are involved in breast and ovarian cancer onset their associations with PARP inhibition have been reported in a number of researches. Because of these details inhibition of PARP has become a vital tool for therapy of various cancers [1]. Against these BRCA genes inhibitors of PARP have shown effective results. PARP inhibitors specifically targets only the cancer cells not normal cells which is their edge point. Conventional therapies have become less famous because mode of action of PARP inhibitor has shown that it is very good against different cancers. [Read the Full Post]

NILOTINIB 

7003 views | Jul 12 2012

ASSOCIATION OF PHILADELPHIA CHROMOSOME WITH CHRONIC MYELOGENOUS LEUKEMIA Philadelphia chromosome is composed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome promotes fusion protein that functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML. [Read the Full Post]

GEFITINIB; A POTENT INHIBITOR OF EGFR

631 views | Jul 11 2012

INTRODUCTION AND MECHANISM OF ACTION There are many inhibitors of tyrosine kinase inhibitors and amongst these Gefitinib is one of the potent inhibitor. It gently inhibits the functions of EGFR or epidermal growth factor receptor. Currently there are two companies are producing Gefitinib including Astra Zeneca Company and Teva Company. Gefitinib Iressa performs its functions by inhibiting EGFR due to its structural properties which contains a ring structure of anilinoquinazoline. Gefitinib EGFR inhibitor costs around 80$ for a vial of 1g and it is available for anyone desired to purchase Gefitinib including researchers, scientists and for laboratory uses. Gefitinib is not soluble in water however Gefitinib solubility can be attained in ethanol, dimethyl sulfoxide (DMSO) and DMF. As far Gefitinib stability is concerned it is stable for a period of 2 years if stored at -20oC. Gefitinib IC50 is 37nM and 57nM for Tyr 1173 and Try 992 respectively. There were many assays were performed for the pharmacokinetics and sensitivity evaluation of Gefitinib. These assays were based on the information of some presumptive markers such as mutated forms of K-Ras and EGFR and variable copy number. Enzyme linked immunosorbent assay (ELISA) is carried out to analyze human serum and study of tissues against a specific drugs or HDRA. This is a competitor inhibitor of EGFR which competes with ATP and binds with ATP binding site present in EGFR which ultimately results in the inhibition of ligand binding and therefore inhibits the signal transduction which is caused by ligand binding. [Read the Full Post]

LENALIDOMIDE – AN ANTI-INFLAMMATORY DRUG

5019 views | Jul 10 2012

LENALIDOMIDE: INTRODUCTION Tumor Necrosis factor (TNF) is a pro-inflammatory cytokine, the high levels of which signify inflammation in several disease conditions like autoimmune disorders (e.g. - rheumatoid arthritis, Crohn's disease and ankylosing spondylitis etc.), numerous cancers, skin diseases like psoriasis and refractory asthma. This is often the rationale that TNF inhibitors are given such importance in medical literature. Starting from natural compounds like curcumin, cannabis and green tea to xanthine derivatives, hallucination inducing compounds and also the best of all monoclonal antibodies, several TNF inhibitors are being studied in several and physiological conditions.As a result of its significance, TNF inhibition in cancers researchers got abundant attention. [Read the Full Post]

TEMSIROLIMUS

3115 views | Jul 10 2012

TEMSIROLIMUS: AN INHIBITOR OF mTOR Protein kinase mTOR are the enzymes that come under the category of phosphatidylinositol 3-kinase or PI3-K that control the cell migration, cell multiplication, cell transcriptional and translational actions and cell survival. The fact that these inhibitors are involved in the above described processes, these enzymes have come into lime light for cancer therapy. In the recent years Temsirolimus mTOR inhibitor has got more popularity as compared to Rapamycin which was used in the late years. [Read the Full Post]

PARP INHIBITOR: TREATMENT OF STROK, ISCHEMIA AND CANCER

3622 views | Jul 08 2012

DEREGULATION OF PARP CASCADE AND ITS APPLICATIONS: Poly ADP-ribose polymerases or PARP are the translated product of PARP genes located in human genome. These proteins play some of the vital roles in the cell such as apoptosis and DNA repair mechanism. The repair mechanism of DNA is specific for the single stranded DNA (ss DNA) breaks. A reasonable work has been reported about the interaction of BRCA1 and BRCA2 and this knowledge leads to the understanding of PARP deregulation causes or links with ovarian and breast cancer as different research reports concluded the mutations of these two genes are present in these cancers. Due to these reasons the PARP inhibition mechanism has become an efficient therapeutic tool for cancer treatment. The specific PARP inhibitors may have efficient results against tumors and cancers with BRCAness. The beauty of these PARP inhibitors is that the normal cells are not affected where tumors cells are only targeted. Mechanism of PARP inhibitor tells about the efficacy of these inhibitors in treatment of cancers and because of their efficient actions the old therapies are becoming less popular as they affect the normal cells as well. [Read the Full Post]