TNO155, an inhibitor of SHP2 exhibit selective sensitivity in OSCC. (A) IC50 of three SHP2 inhibitors (SHP099, TNO155 and RMC4550), were determined for 21 OSCC cell lines using MTT assay. Data shown is mean ± standard deviation (in μM). (B) Correlation plot of PTPN11 CRISPR scores against log10 (lg) IC50 of SHP099/TNO155/RMC4550 IC50 (μM). (C) Dose-dependent effects of TNO155 on two selective “sensitive” lines – ORL-195 and SCC-9; and two “resistant” lines – BICR10 and PE/CA-PJ15 were measured by apoptosis assay. Bar charts show the percentage of apoptotic cells at increasing concentration of TNO155. Error bars are mean±SD of two biological repeats with technical triplicates. Unpaired student's t-test was used with untreated control (0 μM TNO155) as comparator. ∗p: <0.05, ∗∗: p < 0.01, ∗∗∗: not significant (ns). (D) Dose-dependent effect of TNO155 on colony formation assay in sensitive and resistant OSCC cell lines.