Fig. 1: Screening of Kinase inhibitor library for synthetic lethality in HCT116 cell.

A Immunoblot analysis showing loss of ARID1A expression in the two ARID1A-KO clones. B Schematic illustration of the synthetic lethal kinase inhibitor screening. HCT116 ARID1A-WT and ARID1A-KO cell lines were screened in parallel with 430 kinase inhibitor library in an 8-dose titration format. After incubation with the compound library for 72 h, cell viability was determined by Alamar Blue assay. C A −log2 IC50 plot of the screening results. −log2 scale of IC50 values of the drugs against HCT116 ARID1A-KO and ARID1A-WT cells was plotted. D Dose-response curves of HCT116 ARID1A-WT and two ARID1A-KO clones treated with c-MET kinase inhibitor for 72 h are shown. Error bars represent s.d. (n = 3) from three independent experiments. Dose-response curves of HCT116 ARID1A-isogenic cell pair treated with c-MET kinase inhibitors crizotinib (E) and cabozatinib (F) are shown. HCT116 ARID1A-WT, ARID1A-KO #1, and ARID1A-KO #2 clones were incubated with indicated compounds for 72 h and the cell viability was determined by Alamar Blue assay. Error bars represent s.d. (n = 3) from three independent experiments.