Fig. 1.
Development of a KRAS saturation mutagenesis screen for KRAS G12C inhibitors in NCI-H358 (NSCLC) cell model. (A) Schematic diagram of the saturation mutagenesis screen. (B) Western blot analysis of engineered H358 cell lines harboring doxycycline-induced KRASWT, KRASG12D, and KRASG12C/Q61H variants. KRAS relative protein level was quantified from the gel image. (C) Cell viability assays for parental H358 and engineered H358 cell lines harboring KRASG12D or KRASG12C/Q61H in culturing conditions with or without doxycycline induction treated with sotarasib and adagrasib for 7 d (shown as mean ± SD, n = 3). (D) Cell growth curves of H358 parental and engineered H358 cells expressing KRASG12D or KRASG12C/Q61H under continuous treatment using sotarasib (750 nM) or adagrasib (750 nM) for 16 d. Cell confluency images were acquired every 6 h, n = 2.