Extended Data Figure 9. MTH1 inhibitors exert selective toxicity toward transformed cells.

a, BJ cells transformed by KRASV12 or SV40T are more sensitive to the MTH1 inhibitors SCH51344 and (S)-crizotinib than wild type fibroblasts or cells immortalized by telomerase expression. Data are shown as mean ± SEM for three independent experiments (n = 3). b, (S)-Crizotinib does not exhibit any increased unspecific cytotoxicity compared to (R)-crizotinib. In contrast, the (R)-enantiomer significantly impairs the growth of untransformed BJ skin fibroblasts at low micromolar concentrations in a colony formation assay. Compounds were added 24 h after seeding the cells and plates were incubated for 10 days, washed, fixed, and stained with crystal violet. Images are representative of two independent experiments (n = 2). c, IC₅₀ values for MTH1 inhibitors tested against a cancer cell line panel.