Figure 2. Suppression of cell proliferation in response to SAB298 and UM-164.

The results show CellTiter-Glo^® Luminescent Viability Assay and the values are average of triplicate or quadruplet wells, displayed as percent of control assessed at the end of 72 hours treatment ± SE. (A–C) Growth arrest in response to SAB298. The legends on the right provides the IC₅₀, i.e., drug concentrations that reduced cell viability to 50% of the control generated in GraphPad Prism. Black, blue and red lines indicate melanoma cells that are wild-type for BRAF or NRAS (double-wild type), BRAF^V600E/K, or NRAS/HRAS^Q61 mutants, respectively. Green lines indicate ocular melanoma cells with GNA11^Q209L, broken lines are NF1^null (---)_, broken dot broken line are RAC1^P29S/NF1^null double mutant (-.-), and orange line indicates normal human melanocytes that are wild type for all mutations. STDV was about 5% of total count. (D–F) show aligned dot-plot of SAB298 IC₅₀ values, bar graph of increasing levels of IC₅₀ and AUC (Area Under the Curve). Color code as in (A–C). Grey bars indicate melanoma with fusion genes and (H), indicates HRAS^Q61K mutation. (G and H) show comparisons between SAB298 (●) and UM-164 ○ in IC₅₀, AUC1. (I) Tumor growth in response to SAB298. YUSIK tumor bearing mice were treated daily with intraperitoneal injection of 20 mg/kg SAB298 (red) starting on day 12 after injection or with solvent as control (blue). Data are average of 6 mice ± SEM. The p-value of 0.0006 was calculated by Uncorrected Fisher’s LSD using GraphPad based on the last day data. NBMEL; NF1; NF1 and RAC1; GNA11^Q209L; NRAS^G12D; BRAF^G469A.