tcsc0216 Vemurafenib

Vemurafenib (RG7204; PLX4032) is a novel and potent inhibitor of B-RAF kinase, with IC₅₀s of 31 and 48 nM for RAF^V600E and c-RAF-1, respectively.

IC50 & Target: IC50: 31 nM (BRAF^V600E), 48 nM (c-RAF-1)

In Vitro: Vemurafenib (PLX4032) selectively blocks the RAF/MEK/ERK pathway in BRAF mutant cells^[1]. RG7204 is a potent inhibitor of proliferation in those expressing RAF^V600E but not BRAF^WT in 17 melanoma cell lines. Vemurafenib (RG7204) induces MEK and ERK phosphorylation at high concentrations in CHL-1 cells^[2]. Ectopic expression of EGFR in melanoma cells is sufficient to cause resistance to PLX4032^[3].

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^[1]. RG7204 (12.5, 25, and 75 mg/kg, p.o.) significantly inhibits tumor growth and induced tumor regression in mice bearing LOX tumor xenografts^[2].