GDC-0879 INHIBITOR OF MUTATED RAS AND RAF, Sorafenib, angiogenesis inhibitor
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 [2].
GDC-0879: METABOLISM
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.
GDC-0879: PHARMACODYNAMIC STUDIES
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 [4]. 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.
GDC-0879: METABOLISM
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.
GDC-0879: PHARMACODYNAMIC STUDIES
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 [4]. 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.
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