PLX7904

PLX7904 is a potent and selective BRAF inhibitor, with IC₅₀ of appr 5 nM against BRAF^V600E in mutant RAS expressing cells. IC50 & Target:IC50: appr 5 nM (BRAF^V600E, in mutant RAS expressing cells)^[2] In Vitro: PLX7904 inhibits the in vitro growth of two melanoma cell lines (A375 and COLO829) and an additional human colorectal cancer cell line COLO205 that expresses BRAF^V600E with IC₅₀ values of 0.17 μM, 0.53 μM, and 0.16 μM, respectively, on a par with vemurafenib IC₅₀ values in the same assays (0.33 μM, 0.69 μM, and 0.25 μM, respectively)^[1]. PLX7904 and PLX8394 potently inhibit ERK1/2-driven GAL4-Elk1 reporter activity in PRT cells as well as parental cells. PLX7904 and PLX8394 treatment at 1 μM concentration reduce colony formation and viability in parental cells to a similar level as PLX4720^[2]. PPLX7904 potently inhibits phosphorylation of ERK1/2 in mutant BRAF melanoma cells without eliciting paradoxical activation in wild-type BRAF, mutant NRAS melanoma cells. PPLX7904 inhibits ERK1/2 in PLX470-resistant cell lines. PPLX7904 treatment promotes apoptosis and inhibits anchorage-independent growth of vemurafenib resistant cells^[3].