Susceptibility of BRAF mutant melanoma cell lines to MAPK inhibitors. Percent growth inhibition of (A) M238 and (B) M792. After 120 hours treatment with 0–10 μM vemurafenib (V, squares), SCH722984 (E, circles), or the combination (V + E, triangles), cell viability was determined by bioluminescence assay. Results are representative data in duplicate from three independent experiments (n = 6). C. Effect of BRAF-, ERK- inhibition or the combination on MAPK signaling. Cell lines were treated with DMSO (control, C), 500 nM Vemurafenib (BRAFi, B), 500 nM SCH722984 (ERKi, E) or the combination of vemurafenib and SCH722984 (B + E) for 24 hours. Western blots analyzed for phospho- and total MEK, ERK1/2, RSK, AKT and actin as loading control. D. IC50 (nM) to MAPK inhibitors and synergistic effect. BRAF-mutant melanoma cell lines were treated with 0–10 μM vemurafenib (BRAFi) or SCH722984 (ERKi), the combination (B + E) or 0–1 μM trametinib (MEKi). Green indicates sensitivity, yellow intermediately sensitive, and red for resistant. The CI column indicates the combination index of vemurafenib and SCH722984.