Fig. 5.

Bcl-xL expression confers resistance to HDM201. (A) Western blot analysis showing BCL-xL and MDM4 protein expression in PDX models that acquired resistance to HDM201 or CGM097 (res) or were matched vehicle-treated (veh) (9). (B) Score plots for the combination of CGM097 and ABT-263 from an in vitro combination screen on 485 cancer cell lines treated with ranges of concentrations for CGM097 and ABT-263. Cell lines with no TP53 mutation are shown in blue (p53 wt), and cell lines with TP53 modification are shown in green (p53 mt). Boost describes the maximal growth inhibition for any combination vs. the highest single agent activity. (C) Synergistic effect of combinations of HDM201 TP53-MDM2 inhibitor and A-1155463 Bcl-xL inhibitor in the SNG-M cell line. Percent inhibition is shown, each number representing the average of three replicates. Gradient of colors was used for better visualization.