Susceptibility of NRAS-mutant melanoma cell lines to SCH-722984. A. IC50 (nM). Melanoma cell lines containing mutations in NRAS were exposed to 0–10 μM SCH-722984 (black bars) or vemurafenib (grey bars), and the cell viability determined. Results are the mean of three experiments, performed in duplicate (n = 6). Error bars are standard deviation. Bar at 1 μM denotes threshold between sensitive and intermediate. Resistant cell lines have IC50 higher than 2 μM. B. Effects of SCH722984 on MAPK signaling. SCH722984-resistant M202 and SCH722984-sensitive M408 were treated for 24 h with DMSO as solvent control (-) or 500 nM SCH722984 (+). Phosphorylated or total MEK, ERK 1/2, RSK, AKT or beta-actin as loading control were determined by western blot analysis.