Todd Mayhood

Discovery of Novel Oral Covalent Inhibitors Targeting Active GTP-Bound KRASG12C with Potent Antitumor Activity

Current KRASG12C inhibitors mainly target the inactive GDP-bound state, but clinical efficacy is limited, and resistance mechanisms have been identified. We disclose novel covalent inhibitors that selectively target the active GTP-bound KRASG12C. Starting from a high-throughput screen, we identified a keto-indolizine...