DESCRIPTION GDC-0879 is an inhibitor of B-Raf proto-oncogene (BRAF), serine/threonine kinase . It was a preclinical lead compound. PubChem includes four alternative tautomeric forms of this compound. Most sources are linked to CID 11717001 but some assay resulls are linked to CID 57519545. This has a Probe Portal entry SGC GDC-0879 (GtoPdb)

COMMENT The chemotype for this probe is very selective for RAF but is expected to inhibit both mutant and wild-type forms as well as c-RAF. The fact that it is orally bioavailable makes it a very useful probe to interrogate RAF biology. Jun 12 2016 - 4:08am

MOA ATP-competitive inhibitor (Chemical Probes.org)

DESCRIPTION inhibitor of BRAF (Informer Set)

DESCRIPTION Potent B-Raf inhibitor (Tocriscreen Plus)

DESCRIPTION Cyclooxygenase inhibitor; NSAID (Tocris Bioactive Compound Library)

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. (BOC Sciences Bioactive Compounds)