The initial KRAS(G12C) inhibitors reported by Ostrem et al. display more ambiguous characteristics with the conserved water (and the switch-II region), while the later more potent inhibitors are often accompanied with a single isolated high-energy hydration site. Only a subset of covalent inhibitors is capable in displacing the Thr58 associated conserved water. One of these inhibitors, adagrasib, was shown to bind WT KRAS with higher affinity than sotorasib .