Fig. 1
S63845 binds MCL-1 and induces apoptosis in several cancer cell lines. a S63845 exhibits a concentration-dependent shift in MCL-1 stabilization in a thermal stability assay. b S63845 and A-1210477 exhibit concentration-dependent apoptosis, as assessed by PS externalization using flow cytometry, in MCL-1-dependent cell lines, H929 and U-2946 after 4 h of exposure. c S63845 and A-1210477 fail to induce apoptosis in a BCL-XL-dependent cell line, K562, at 4 h, unlike A-1331852 (positive control). d MAVER-1, a BCL-2 dependent cell line, when exposed to the indicated BH3 mimetics for 4 h resulted in enhanced apoptosis. e Jurkat cells (wild type and deficient in the specified proteins), exposed to increasing concentrations of S63845 for 24 h exhibited caspase-9-dependent apoptosis. f Primary cells isolated from CLL patients, exposed to the indicated BH3 mimetics for 8 h, exhibited varying extents of apoptosis. g ABT-199 but not S63845 exhibits a concentration-dependent shift in BCL-2 stabilization in a thermal stability assay. Error bars = Mean ± SEM (standard error of the mean); *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001
