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There are various reasons of cancer formation but most of cancers are associated with mutated MAP kinase pathway. GDC-0879 is among such inhibitors which can inhibit this mutated kinases pathway. This important pathway initiates from RAS and leads to the other downstream kinases including Raf, MEK and ERK. Therefore the compounds which can inhibit this signaling pathway is very interesting to the researchers. Those inhibitors which are active against the MEK kinases are mostly not effective against the mutated forms of RAS. The screening of compound library leaded to the discovery of GDC-0879 which checks growth of tumor cells having Ras gene mutations. GDC-0879 is a competitor inhibitor of Raf kinase, its activity depends on the concentration of ATP that is substrate for most of the kinases including Raf. Few inhibitors such as Vemurafenib are efficient in the treatment of cancerous cells having BRAF V600E mutation. Inhibitors of MAP kinase pathway are able to arrest the actions of mutated kinases and check the tumor growth in Ras activation mechanism. Secondly WT-Raf is activated by the actions of GDC-0879. Due to this dimerization and localization is stimulated in the membrane region. As a result RAS-GTP interaction is increased. These effects are related to the Raf kinase domain. This compound is promising in those cell which show specific mutations in the BRAF gene. Various cancers are linked with the BRAF kinase abnormal activation. GDC-0879 actions were studied by the levels of phosphorylation of MEK1/2 and ERK1/2. These levels are acted as biomarkers for the inhibitory effects of GDC-0879 on growth of tumor cells. This mechanism also enhanced the existance of the mutant cell. BRAFV600E mutations were specifically targeted by this inhibitor. The time of tumor growth was elapsed due to the actions of this inhibitor. Another compound having multiple effects on MAP kinase pathway is Sorafenib. The PDGFR and VEGFR levels are also regulated by GDC-0879; therefore it is an angiogenesis inhibitor. It also controls the genetic expression of PI3K pathway. Compounds inhibiting the MEK activity are able to arrest the growth of cancer not matter if these cells have the WT BRAF mutation. These findings proved that the Raf pathway arresting can be able to check the tumor effects. The GDC-0879 metabolism and removal from the cell was studied in different species of animals for example rat, mice, dog and monkey. Rats were having faster removal rate than in dogs. However monkeys and mouse had normal rates. Its half life is between 0.28 H – 2.97 H. This is orally bioavailable and the products of its metabolism are ketone bodies. Hence it is proved by in vivo studies that the removal of this kinase inhibitor depends on the type of animal or physiological conditions. Various inhibitors of Raf kinases such as RAF265 were also tested for the pharmacodynamic studies. A limited knowledge of the inhibitory effects on MEK downstream kinases is available. Xenograft model A375 was also analyzed to notice the plasma levels of GDC-0879. It was found that it can inhibit the pMEK1 or MEK at very low concentration that is 3.06 ?M concentrations. Preclinical studies are very helpful in understanding the role of various mutaitons in the cancer formation. CONCLUSION In a nut shell, GDC-0879 is a kinase inhibitor which specifically targets the BRAF V600E mutation. A good number of tumors and cancer are associated with this mutation. So this compound is effective against many types of malignancies or solid tumors. It regulates MAP kinase pathway by targeting K-Ras. As one of the world leading suppliers of high-performance life-science products. We have over 8,000 products which consist of inhibitors, antibodies, RNAis, proteins and peptides those which focus on signaling pathways such as CP-690550, MDV3100, XL184 & so on. Furthermore, compound libraries for high-throughput screening and high-content screening are also available.
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