KRAS and neoplasm: In the G12S ligand, an electrophilic group, β-lactone, specifically reacts with a serine residue and has been attached to the tetrahydropyridopyrimidine moiety of the G12C ligand Adagrasib.283 The G12S covalent ligands, G12Si-1/5 exhibit inhibitory effects to both KRAS GTP-loading and phosphorylation of downstream ERK in tumor cell lines containing KRAS G12S mutation.