3. The Astellas KRASG12C covalent inhibitor, ASP2453, is an oral molecule with activity in preclinical mouse models of KRASG12C-mutated cancer at lower doses than sotorasib (AMG 510). Several KRAS inhibitors have been highlighted recently. ASP2453 possesses an interesting spirocyclic azetidine-containing acrylamide warhead, and the authors note that ASP2453 is likely more reactive than piperazine-bearing AMG 510. ASP2453 does not appear to have entered clinical development yet.