Fig. 5: S63845 combined with ABT-263 or A-1331852 were potent to kill melanoma cells resistant to current therapies.
From: MCL1 inhibitors S63845/MIK665 plus Navitoclax synergistically kill difficult-to-treat melanoma cells
Cell lines include patient samples relapsed from targeted therapy or anti-CTLA-4/PD-1 immunotherapy, or those with acquired resistance to a BRAF inhibitor (Vemurafenib) or a MEK inhibitor (Trametinib), which were created using A375 and SKMEL-28 melanoma lines. a ATP assay. b IncuCyte live cell imaging with active Caspase 3/7 for quantification of apoptosis. Images were acquired using the phase and green fluorescent channels every 4 h for a total of 48 h. For visual clarity, we marked only the combinational treatments that were significantly different from comparisons with the DMSO and the single-drug treatments. Both the combinations (S63845 plus A-1331852 in (a), or S63845 plus ABT-263 in (b)), significantly (***indicates p < 0.001) reduced cell viability and increased apoptosis compared with DMSO or with single drug treated conditions in all melanoma cell lines at sub-micromolar doses. For visual clarity * is not shown in the figure for (a). Error bars represent ± SEM. For (b) the same color represent the same treatment condition for the line and the bar graphs.
