Discovery of -(1-Acryloylazetidin-3-yl)-2-(1-indol-1-yl)acetamides as Covalent Inhibitors of KRAS.

KRAS regulates many cellular processes including proliferation, survival, and differentiation. Point mutants of KRAS have long been known to be molecular drivers of cancer. , which occurs in approximately 14% of lung adenocarcinomas, 3-5% of colorectal cancers, and low levels in other solid tumors, represents an attractive therapeutic target for covalent inhibitors.