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Blog of Signaling Pathways

HDAC INHIBITORS AGAINST TOMORS

4159 views | Aug 22 2012

HDAC INHIBITION: A SOURCE OF EPIGENETIC MODULATION Histone acetylation is an essential process in functions like cell growth and cellular death by causing the inhibition of transcription of proteins caused by removal of the acetyl groups from the histone proteins, as a result of which the binding of DNA is increased, causing it to be condensed. A disturbance in this phenomenon leads to an uncontrolled growth of the cells that leads to the production of tumors and neurodegenerative diseases as well. HDAC inhibition is performed to treat various forms of tumors by using HDAC-2 inhibitors. Different successful studies at various levels have elucidated the mechanism of action of HDAC inhibitors leading to their enormous applications in various preclinical and clinical trials. The levels of HDAC inhibitors can be assessed by the use of different sort of assays specially developed for this reason. These chemical assays can be performed in laboratory by using various kits. The researchers can perform nonisotopic HDAC inhibitor and microplate reader compatible assay and the one for the robotic screening and compound profiling. In addition to it a simple flourogenic assay can also be used for the high-throughput screening process. [Read the Full Post]

COMPOUND LIBRARY AND ITS BENIFITS

3087 views | Aug 21 2012

THE BASIC CONCEPT OF COMPOUND LIBRARY: The collection of data about different compounds at a place where all these compounds can be analyzed by the good worth of their storage is known as a compound library. Hence compound library is basically a collection or arrangement of different compounds. The maintenance, storage and placing of these screening compounds is actually a proper scientific way. The development of different new and emerging technologies in designing and managing of a chemical screening library has brought very remarkable success and changes in the procedure of drug discovery and these new changes have a great and positive impact on the ongoing research on drug discovery [1]. The most determining and crucial step in this procedure of compound library screening is the selection of biologically relevant and useful compounds and molecules that is usually guided by some experts of this area who would must devise some detailed protocols and schemes to make this process of selection faster, more efficient and better than ever in generating a resourceful research chemicals library. State-of-the-art methodologies that include both the fragment-based library designing and the structure-based small molecule library designing procedure is supported by the latest and efficient software tools which ensure a promising implementation of a small molecule drug screening library. [Read the Full Post]

c-MET INHIBITORS IN CANCER TREATMENT

4608 views | Aug 20 2012

c-MET AND ITS INHIBITION: c-Met is encoded by a proto-oncogene and is also known as HGF-R or hepatocyte growth factor receptor. As it is a proto-oncogene, therefore, its hyperactivation is involved in development of different cancers. c-Met is known to form new blood vessels in growing tumors and hence help their invasion to other tissues. Different examples of cancers involving c-Met aberrant behavior are stomach cancer, liver cancer, breast cancer, thyroid cancer, ovarian cancer and brain cancer. Because of involvement of this particular oncoprotein in many cancers, it has remained target in lots of research related to anti-cancer therapy. Lots of c-Met antagonists have been developed and one of the examples is c-Met inhibitors that has been implicated clinically and therapeutically. Different other antagonists and agonists of c-Met are also being used in order to get an understanding about different functions of c-Met and the types of interactions that it has with other molecules in the signaling cascade. Many of the c-Met inhibitors are commercially available at reasonable prices for example tyrosine kinase inhibitor. These inhibitors can be easily bought from the suppliers for any purpose. [Read the Full Post]

COMPOUND LIBRARIES AND THEIR ADVANTAGES

3843 views | Aug 19 2012

COMPOUND LIBRARIES: INTRODUCTION AND FUNCTIONS A fair to a big group of the stored compounds which can be used for industrial manufacturing of drugs or the high-throughput screening assay based drug discovery, is defined as a compound library. This collection or group of compounds is supported by the specific kind of database that contains the relevant information and knowledge about the included compounds and that information includes the compound’s purity, preparation, chemical structure, chemical, physical and pharmacological properties [1]. A lot of compound libraries are commercially available and they might contain a mixture of some common or some unique biochemical compounds. A detailed file containing the complete information regarding the compounds is presented in the research chemical library and this file is purchasable from the relevant suppliers. These compound libraries are most advantageous in the high throughput screening assays in which the target of a drug is screened against a number of different compounds that are taking space in the library. More the number of compounds in a compound library more are the chances of getting a ‘hit’ in screening compound procedure. [Read the Full Post]

EGFR INHIBITORS IN CANCER THERAPY

4606 views | Aug 17 2012

EGFR AND DEVELOPMENT OF CANCER: Among a variety of signal transduction pathways vital for cell survival, growth, and proliferation etc. EGFR pathway is considered to be quite important. Its importance has been judged by analyzing the processes like tumor development and some other diseases occurring due to uncontrolled growth of cells. Mostly EGFR signaling pathway malfunctioning has been linked with the development of such types of diseases in the body for example; colon cancer, breast and lung cancer and with anal cancer, multiform Glioblastoma and epithelial cancer. Therefore targeting EGFR for cancer therapy is a feasible approach. This EGFR inhibiting strategy magnifies the HER-1inhibitor and its importance. These inhibitors have a very significant role in the patients’ survival from the disease. Different EGFR agonists and antagonists are used for the purpose of unveiling the role of this molecule in the cell as well as looking for a most efficient EGFR inhibitor. These inhibitors are available at a very reasonable price and can be bought for any purpose. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

4788 views | 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]

HDAC INHIBITORS AGAINST CANCERS

3957 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

2440 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

2390 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

3997 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

3615 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

2938 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

2717 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

3308 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

3411 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

4539 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

3772 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

3177 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

3001 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

4217 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]