Fig. S9.

Bcl-xL modulates the sensitivity of cell lines to TP53-MDM2 inhibition. (A) Shift of sensitivity to HDM201 treatment in WM226.4, a p53 wild-type melanoma cell line, transiently transfected with Bcl-xL, compared with cells transfected with a control plasmid. The curve is representative of two independent experiments of a 3-d cell viability assay. The IC₅₀ was sixfold higher on average on Bcl-xL expression. The Western blot shows expression of Bcl-xL after transient transfection in WM226.4 cells. (B) Synergistic effect of combinations of HDM201 TP53-MDM2 inhibitor and A-1155463 Bcl-xL inhibitor in two cell lines. SNG-M cells (Upper) and LS-513 cells (Lower) were treated for 3 d with a 7 × 7 dose matrix of HDM201 and A-1155463. (Left) Percent inhibition, with each field representing the average of three replicates. (Right) The additional (or reduced) effect level, in percent, relative to drug self-combinations based on the Loewe model.