A KRAS protein bearing cysteine in place of glycine at residue 12. The introduced cysteine permits selective covalent chemistry at a suitable pocket; this strategy does not automatically apply to other Ras mutations.
A covalent inhibitor developed against KRAS G12C protein, also called sotorasib. Its state-dependent binding illustrates targeting a mutant small GTPase outside the nucleotide site.[ref]
The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity by Jude Canon and others. Chemical and preclinical characterization
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