When administered at a dose of 150 mg/kg/day, PLX8394 substantially reduces tumor growth and MAPK pathway signaling, as well as tumor cell proliferation in H1755 xenograft tumors, demonstrating its efficacy without causing overt toxicity in mice. The combination of PLX8394 with CP-358774 results in plasma concentrations of CP-358774 exceeding 1 μM^[2].

PLX8394 is an orally active BRAF small molecule inhibitor with IC50 of 3.8 nM for BRAF(V600E), 14 nM for WT BRAF and 23 nM for CRAF. It has potential antitumor activity^[1].

PLX8394 is a potent inhibition of ERK1/2 phosphorylation in cells at concentrations above 25 nM, and in parental cells at a lower threshold of 10 nM. This compound effectively diminishes levels of cyclin D3 and cyclin D1, phosphorylation of retinoblastoma protein, and expression of cyclin A2 in both parental and PRT cells. Additionally, PLX8394 is capable of inhibiting ERK1/2 phosphorylation and growth in PLX4032-resistant cells that possess a BRAF V600K/L505H double mutation or a transposon-induced, N-terminal truncated form of BRAF^[1].

PLX8394 also significantly reduces tumor cell growth and curtails MAPK signaling in LA cell lines harboring either the endogenous V600E mutation or non-V600 mutant forms of BRAF^[2].