KRAS is commonly mutated in a broad spectrum of cancers; the KRAS-G12C mutation commonly occurs in non-small-cell lung cancer (NSCLC), and is also found in several other cancer types (albeit at lower frequency), such as pancreatic ductal adenocarcinoma (PDAC) and colorectal adenocarcinoma. The first selective KRAS-G12C inhibitor was reported in 2013 by Ostrem et al., but identifying similar inhibitors with properties suitable for clinical development has proved challenging. Two papers have now reported the discovery and preclinical analyses of two different covalent inhibitors of KRAS-G12C (AMG 510 and MRTX849) as well as the first data on the efficacy of these inhibitors in cancer patients.
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