Vemurafenib

Vemurafenib (PLX-4032;RG7204;RO5185426) is a potent, selective B-RAF V600E inhibitor with IC50 of 30 nM, displays similar potency for c-RAF-1 (IC50=48 nM), and has selectivity against many other kinases, including wild type B-RAF (IC50=100nM); potently inhibits proliferation of a panel of tumor cell lines, selectively blocks the RAF/MEK/ERK pathway in BRAF mutant cells; causes tumor regressions and improves animal survival in tumor xenograft models of BRAF(V600E)-expressing melanoma.Skin Cancer Approved(In Vitro):Vemurafenib (PLX4032) selectively blocks the RAF/MEK/ERK pathway in BRAF mutant cells. RG7204 is a potent inhibitor of proliferation in those expressing RAFV600E but not BRAFWT in 17 melanoma cell lines. Vemurafenib (RG7204) induces MEK and ERK phosphorylation at high concentrations in CHL-1 cells. Ectopic expression of EGFR in melanoma cells is sufficient to cause resistance to PLX4032.(In Vivo):Vemurafenib (PLX4032, 20, 25, 75 mg/kg, p.o.) causes dose-dependent inhibition of tumor growth, with higher exposures resulting in tumor regression of BRAF mutant xenografts. RG7204 (12.5, 25, and 75 mg/kg, p.o.) significantly inhibits tumor growth and induced tumor regression in mice bearing LOX tumor xenografts.