|Description||GDC-0879, a highly selective, potent, and orally bioavailable RAF small-molecule inhibitor. In GDC-0879-treated mice, both cell line- and patient-derived BRAF(V600E) tumors exhibited stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared with mutant KRAS-expressing tumors. Despite the involvement of activated RAF signaling in RAS-induced tumorigenesis, decreased time to progression was observed for some KRAS-mutant tumors following GDC-0879 administration. Moreover, striking differences were noted for RAF and MEK inhibition across a panel of 130 tumor cell lines. Whereas GDC-0879-mediated efficacy was associated strictly with BRAF(V600E) status, MEK inhibition also attenuated proliferation and tumor growth of cell lines expressing wild-type BRAF (81% KRAS mutant, 38% KRAS wild type). The responsiveness of BRAF(V600E) melanoma cells to GDC-0879 could be dramatically altered by pharmacologic and genetic modulation of phosphatidylinositol 3-kinase pathway activity. These data suggest that GDC-0879-induced signaling changes are dependent on the point of oncogenic activation within the RAS network. Taken together, these studies increase our understanding of the molecular determinants for antitumor efficacy resulting from RAF pathway inhibition and have implications for therapeutic intervention in the clinic.|
MLN2480 is an oral, selective pan-Raf kinase inhibitor. The Raf kinases (A-Raf, B-Raf and C-Raf) are key regulators of cell proliferation and survival within th...
PLX7904, also known as PB04, is a potent and selective paradox-breaker RAF inhibitor. PB04 is able to efficiently inhibit activation of ERK1/2 in mutant BRAF me...
AZ628 is a potent, ATP-competitive inhibitor of Raf kinases (IC50 values are 29, 34 and 105 nM for c-Raf1, B-RafV600E and wild-type B-Raf, respectively). It dis...
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aA B-Raf inhibitor, pyrazine and pyrrolo[2,3-b]pyridine derivatives, useful in the treatment of cancer and proliferative diseases.
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B-Raf IN 1
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Locostatin is a Raf kinase inhibitory protein (RKIP) inhibitor that disrupts the interaction of RKIP with Raf-1 kinase and GRK2. Locostatin is also an inhibitor...
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B-Raf inhibitor 1
B-Raf inhibitor 1 is a potent and selective B-Raf inhibitor with cell IC50s of 0.31 μM and 2 nM for A375 proliferation and A375 p-ERK respectively.
GDC-0879, a highly selective, potent, and orally bioavailable RAF small-molecule inhibitor. In GDC-0879-treated mice, both cell line- and patient-derived BRAF(...
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ZM336372 is a Raf-1 activating agent, has been shown to cause growth inhibition and suppression of hormone secretion in a neuroendocrine cell line. ZM336372 cau...