Blog of Signaling Pathways


3363 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]


2802 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]


3649 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]


3268 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]


3311 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]


2982 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]


3423 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]


6117 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]


606 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]


4375 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]


2708 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]


3172 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]

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

9856 views | Jul 04 2012

CHARACTERISTICS OF DASATINIB The amplified death rate because of cancer and multidrug resistance development in cancer cells for existing drugs are the persuasive force for the researchers as well as scientists to explore new drugs that have better efficiency. Each cellular system is organized by a diversity of controllers called cell cycle regulatory proteins.Cancer cells have the capability to mutate themselves in a variety of ways which make them to detour the action of a specific drug. Another concern with the cancer is that it metastasizes. Other difficulty with the chemotherapy of cancerous cells is toxicity. So considering afore mentioned problems it is evident and compulsory to search for new drugs. Due to above mentioned problematic effects of Imatinib which has been administered for years induces scientists to search for a more mild and more active drug. In this matter a new drug called Dasatinib was discovered by Jagabandhu Das. In contrast to Imatinib, Dasatinib BMS 354825 became renowned due to its lesser harmful and more efficient nature. This drug was discovered by Squibb Company and it is sold as Sprycel. [Read the Full Post]


3147 views | Jul 03 2012

TEMSIROLIMUS: mTOR INHIBITOR mTOR belongs to phosphatidylinositol 3-kinase family which are the protein kinases that regulate cell survival, growth, proliferation, transcriptional activities, cell migration and protein synthesis. Due to the involvement of these in above mentioned processes they have gained importance from therapy point of view in cancer treatment. In comparison to Rapamycin Temsirolimus mTOR inhibitor gained importance for the past few years. [Read the Full Post]


2325 views | Jul 02 2012

TEMSIROLIMUS ASmTOR INHIBITOR mTOR belongs to phosphatidylinositol 3-kinasefamily which are the protein kinases that regulate cell survival, growth, proliferation, transcriptional activities, cell migration and protein synthesis. Due to the involvement of these in above mentioned processes they have gained importance from therapy point of view in cancer treatment. In cosmparison to RapamycinTemsirolimus mTOR inhibitor gained importance for the past few years. [Read the Full Post]


3420 views | Jul 01 2012

BORTEZOMIB: INTRODUCTION In cell among the tiny organelles proteasomes are the foremost vital ones. They play necessary role in the correct regulation of the cell cycle by removing the proteins that don't seem to be necessary for cell. In cancer cell it rarely happens that the proteins which are involved in the controlling the dysregulated growth of the cells are excised by proteasomes. A promising target for the therapy of cancer is to inhibit proteasomes so that the uncontrolled growth is inhibited. A variety of compounds were typically used for cancer therapy that inhibits proteasomes. Among them EGCG additionally referred to as Epigallocatechin-3-gallate, Disulfiram and Salinosporamide-A that are present in green tea were used. The primary inhibitor of proteasomes that got approved to enter clinical trials for cancer therapy is Bortezomib. [Read the Full Post]


5832 views | Jun 28 2012

CHRONIC MYELOGENOUS LEUKEMIA AND PHILADELPHIA CHROMOSOME During meiosis if BCR and tyrosine kinase ABL are unable to separate and fuse together it leads to condition called Philadelphia chromosome. Due to the fusion of these genes it leads to translation of abnormal protein which acts as malfunctioned tyrosine kinase that makes it oncoprotein. Around 90% of patients suffering from Ph+ also suffer from chronic myelogenous leukemia or CML. This fusion protein is being targeted for therapy of cancer since it is involved in CML and various researches are being carried out in this regard. An inhibitor of this protein is Nilotinib bcr-abl inhibitor which is used to treat CML. [Read the Full Post]


2644 views | Jun 29 2012

EVEROLIMUS: INTRODUCTION mTOR pathway is among the different vital regulators of cell cycle which are involved in its regulatory activities likecell proliferation, growth, migration and activities related to transcription and translation. mTOR is the translational product of FRAP1 gene which phosphorylates threonine/serine residues in protein. Defected or dysregulated mTOR pathway is a common reason of developing cancerous cells. Therefore, these proteins are also targeted while looking for an effective anti-cancer therapy. Everolimus mTOR inhibitor is among the efficientinhibitors that have been searched so far. Afinitor Everolimus is the brand name of inhibitor and developed by Novartis. Everolimus structure contains 40-O-(2-hydroxyethyl) derivative and properties related to ispharmacokinetics are found to be improved by the presence of oxygen at position 40. Everolimus IC50 for mTOR is around 1nM. Everolimus solubility is 100mg per ml of DMSO while it is also soluble in ethanol and water. It is administered orally and Everolimus price $60 in packaging of 5mg.It is distributed in dry ice. [Read the Full Post]


3159 views | Jun 27 2012

SORAFENIB: INTRODUCTION Various kinds of non-receptor tyrosine kinases or receptor tyrosine kinases (RTKs) are available in the cells which are employed in responding to intra or extracellular stimulusby carrying out either initiatory or inhibitory action on various signaling pathways. Any sort of problem in this process may cause cancer. Inhibition of kinase enzymes to prevent some mal-expressed or over-expressed gene causing cancer is found to be an effective tool. Inhibition of various kinases is being done by using single inhibitor. Since malfunctioned tyrosine kinases are involved in onset of cancer, research is being done on their inhibitors for cancer therapy.Many of them are giving promising results in their clinical trials.An important example of these inhibiting drugs is Sorafenib VEGFR inhibitor that has been found to inhibit the protein kinases except respective VEGFR. When SorafenibRaf inhibitor was given Raf/MEK/ERK pathway was found inhibited. [Read the Full Post]


4015 views | Jun 26 2012

HDAC INHIBITIORS AND EPIGENEITIC MODULATION: Histone proteins are major part of cellular genome and acetylation of these proteins plays a mile stone role in some of the most important cellular mechanisms such as growth of cell and cell death by apoptosis. The process which controls apoptosis process is carried out by checking the gene transcription of different important proteins by removing acetyl groups from histones, this deacetylation leads to condensation of DNA due to increasing capacity of DNA binding. In neurodegenerative diseases this mechanism of deacetylation goes wrong leading to various types of cancers in which cell proliferation is uncontrolled. This problem leads to the HDAC inhibitor pathway and smoothes the process of HDAC inhibition. HDAC inhibitions have been employed in preclinical and clinical studies due to which extensive and successful use of this process is targeted by many researchers. HDACs levels estimation has been developed by different activity assays. These assays are carried out by manually in the research lab or by kit methods. A nonisotopic assay that is microplate reader compatible can also be performed by researchers for the analysis of HDAC inhibitors, an appropriate test for compound profiling and robotic screening or a suitable fluorescence assay for high-throughput screening. [Read the Full Post]