Supplementary Figure S1 shows IC50 values of KRASG12C inhibitors for KRASG12C, NRASG12C, HRASG12C. Supplementary Figure S2 shows inhibition of NRASG12C by sotorasib in 293T and MOLT-4 cells. Supplementary Figure S3 shows effect of amino acid substitutions in NRASG12C or KRASG12C on signaling in response to sotorasib and adagrasib. Supplementary Figure S4 who's location of isoform-variable residues relative to Switch-II binders. Supplementary Figure S5 shows crystal structures of KRASG12C inhibitors and interactions with His95. Supplementary Figure S6 shows chemical structures of switch-II pocket-binding KRASG12C inhibitors. Supplementary Figure S7 shows structural model of sotorasib interaction with Leu95.
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Rubinson et al. (2024) studied this question.
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