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Blog of Signaling Pathways

HDAC INHIBITORS AGAINST CANCERS

3856 views | Aug 15 2012

HDAC INHIBITION AND EPIGENETIC MODULATION An important process; histone acetylation is related to cellular functions for example cell death and cell growth stimulating the protein transcription inhibition by removing the acetyl groups from the related proteins hence causing the increase in DNA binding and making it more condensed. Any disturbance in this process leads to the uncontrolled cellular growth that further leads to the tumor production and also the neurodegenerative diseases. Histone deacetylase inhibition is carried out for the treatment of different types of tumors by using the HDAC-6 inhibitors. Various successful studies at different levels have exhibited the mode of action of histone deacetylase inhibitors further leading to their vast area of applications in different clinical and pre-clinical studies. The HDAC inhibitors levels can be analyzed by using various types of assays specifically developed for this purpose. These assays can be carried out in the labs through different kits. Researchers can perform microplate reader compatible assay and the nonisotopic HDAC inhibitor assay and also the one for compound profiling and robotic screening. In addition to this simple flourogenic assay may also be carried out for the process of high-throughput screening. [Read the Full Post]

MEK PATHWAY INHIBITION FOR CANCER THERAPY

2397 views | Aug 13 2012

SIGNALLING OF MEK PATHWAY: Various types of cells exist on the surface of the cells helping the cells to coordinate with the environment and the other cells. The growth factor receptors are such receptors which after getting triggered by the ligands usually play a very vital role in the process of cell signaling hence stimulate different pathways that are necessary for the cell survival and growth. One such example is MEK kinase cascade that plays an important role in pro-survival signaling. The inhibition of MEK kinase pathway is one of the attractive strategies when there is a need to inhibit un-necessary proliferation of cells in case of cancer. It has been studied that MEK signaling pathway gets hyperactivated in the cancer cells, so scientists devised a good therapeutic tool against cancer by designing different inhibitors of MEK pathway. 20 years ago, the structural properties of MEK molecule were described [1], which make the approach of scientists much easier for specific MAP2k2 inhibitor. [Read the Full Post]

INHIBITING mTOR IN CANCER THERAPY

2331 views | Aug 14 2012

SIGNALLING VIA mTOR: mTOR is serine/threonine kinase protein and stands for “mammalian target of Rapamycin”. It also known as FRAP1 i.e., FK506-binding protein 12 - rapamycin associated protein-1. It as encoded by a gene known as FRAP1.mTOR is known to be involved in controlling various cellular processes for example; cell growth, survival, proliferation, transcriptional regulation and migration of proteins. mTOR regulatory proteins function in these processes by responding to the energy and nutrient status of the cell. As mTOR is involved in lots of cellular processes regarding its growth proliferation and survival, it can provide a target in cancer therapy; therefore, mTORc1 inhibitors have been designed that can control the cancer progression and development by inhibiting the functions mTOR performs. Inhibiting mTOR signaling pathway thus controls the tumor growth and limits tumorigenesis. [Read the Full Post]

IGF-1R INHIBITOR IN CANCER TREATMENT

3904 views | Aug 12 2012

SIGNALING PATHWAY AND CANCER: One of the important signaling molecules in body of human cells is the Insulin like growth factor 1 and abbreviated as IGF-I and also known as sulfation factor or somatomedin. Structure of this protein, as indicated by the name, resembles insulin and responsible of stimulating a signaling pathway through transmembrane receptor protein i.e., receptor IGF-1. The receptor is very much important for its role in process of aging and signaling of insulin. IGF-1 receptor is also connected to different types of tumors like breast cancer, lung cancer and prostate cancer. It was observed that this receptor offers resistance against chemotherapy and radiotherapy in the cells hence showing the anti-apoptotic activity. An important example of such resistance is Erlotinib, HER-1 inhibitors that is used against breast cancer and causes inhibition of EGFR signaling pathway but IGF1 receptor in cells generates resistance against this drug. The formation of hetrodimers has been reported that stimulate the EGFR cascade to further continue rather than its inhibition. [Read the Full Post]

INHIBITON OF AKT FOR THE TREATMENT OF CANCER

3515 views | Aug 10 2012

CELL PROLIFERATION AND AKT PATHWAY Signal transduction pathways involve various types of kinase enzymes. AKT kinase is such an enzyme that is responsible of phosphorylating the proteins on their specifically serine/threonine sites specifically. It is also named as PKB which means Protein kinase B. It is involved in different kinds of cellular processes like apoptosis, transcription, translation, metabolism and the most important of above all is the cell proliferation and cell migration. Many cancerous cells have been found to exhibit AKT dysfunction therefore it is thought to have an important role in the regulation of cell cycle. AKT pathway gets active by stimulation from PI3K and it also activates by itself mTOR protein to initiate the further process. When PI3K gets hyperactivated, there is an increase in rate of cell division process etc. hence caused tumorigenesis. As compared to any other pathway of signal transduction, this AKT pathway exists more frequently in the cancer cells due to event of amplification, mutation and translocation in its kinase proteins. To fight against various types of cancers and tumors the strategy applied is to target any one of these kinase proteins of this pathway and the AKT inhibitors were found quite good to be used for the treatment of cancer. [Read the Full Post]

CANCER INHIBITION BY CDK

2844 views | 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]

MEK INHIBITOR AGAINST UNCONTROLLED GROWTH OF CELLS

2662 views | Aug 07 2012

MEK – RECEPTORS: Growth factor receptor is found on the surface of cells and upon stimulation a protein is encoded in the nucleus which is vital for cell signaling. A type of kinases is called MEK that is important for the pro-survival signaling. An easy approach to hinder or control the pro-survival signaling is the inhibition of MEK which can be done by designing MEK kinase inhibitor. The most suitable example of is of cancer cells which is characterized by uncontrolled cell proliferation and in these cells MEK signaling pathway is found as hyperactivated, hence the introduction of MEK pathway inhibitors is the appropriate therapy. About 20 years back the structure of MEK was elucidated, due to this researcher are aided well for the development of specific MEK inhibitors. [Read the Full Post]

INHIBITON OF AKT TO FIGHT CANCER

3217 views | Aug 06 2012

AKT PATHWAY AND CELL PROLIFERATION Different types of kinases are involved in the signal transduction pathways. AKT kinase is one such kinase that specifically phosphorylates proteins at their serine/threonine amino acids site. It is also called as PKB i.e., Protein kinase B and is involved multiple types of cellular processes e.g., glucose metabolism, transcription, translation, apoptosis and important of all cell proliferation and its migration. Many of the cancer cells have been found to have AKT dysfunction in them therefore it is considered to have a very important role in cell cycle regulation. AKT gets activated by PI3K and activates itself mTOR protein and further process in the cell gets initiated. Hyperactivation of PI3K increases the rate of cellular process of division etc. and hence takes part in tumorigenesis. This pathway is more frequently found in cancer than any other signal transduction pathway due to the occurrence of mutation, translocation and amplification in its protein kinases. Targeting one of the kinases of this pathway is the strategy to fight against many types of cancers and PKB inhibitors have been found to be quite feasible to be used against cancer. [Read the Full Post]

IGF-1R INHIBITION AND CANCER TREATMENT

3331 views | Aug 05 2012

SIGNALING IN CANCER: In humans a gene IGF-I encodes a protein known as insulin like growth factor 1 or abbreviated as IGF-1, this is also known as sulfation factor or Somatomedin. The name related to insulin is due to the structural similarities with insulin. This protein is responsible for the activation of a signaling pathway downstream to it and this is done by triggering IGF receptor known as IGF-1 receptor which is a transmembrane receptor. This receptor plays important roles in aging and insulin signaling but many reports are also there which have proven the connection of IGF1-R with many cancers for example prostate cancer, lung cancer and breast cancer as well. This receptor also provides resistance against chemotherapy and radiotherapy, hence showing anti-apoptotic characteristics. To this statement one example is of breast cancer where EGFR inhibitors such as Erlotinib are used for the EGFR signaling pathway checking but here IGF1-R produces resistance against Erlotinib by the formation of a heterodimer which tends the EGFR pathway continue regardless the presence of inhibitor. The link between EGFR and IGF-R is also noted in the breast cancer where angiogenesis resulted in the tumor invasion or metastasis. So, inhibition to IGF1-R is a way to abrogate many signaling pathways leading to malignancies. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

4387 views | 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]

HDAC INHIBITORS AGAINST CANCERS

3630 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

3119 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

2912 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

4090 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

2688 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

5327 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

2743 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

3619 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

3321 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

2752 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]