Discovery and Optimization of a Potent, Efficacious, and Brain-Penetrant Inhibitor of KRAS G12C.

doi:10.1021/acs.jmedchem.5c02279

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Article

Discovery and Optimization of a Potent, Efficacious, and Brain-Penetrant Inhibitor of KRAS G12C.

Journal of medicinal chemistry - 12 Mar 2026

Landry Matthew L, Malhotra Sushant, Beresini Maureen, Chan Connie, Chan Emily, de la Cruz Cecile C, Endres Nicholas F, Evangelista Marie, Gustafson Amy, Hu Dennis, Hunsaker Thomas, Hsu Peter, Izrayelit Yevgeniy, La Hank, Saenz-Lopez Larrocha Pablo, Lian Qihui, Merchant Mark, Mao Jialin, Mroue Rana, Oh Angela, Plise Emile, Shao Cheng, Siu Michael, Tran John C, Wang Yanguang, Wang Weiru, Wei Binqing, Wong Susan, Yen Chun-Wan, Zhou Yuhui, Purkey Hans E, Heffron Timothy P, Salphati Laurent

Abstract excerpt

Mutant KRAS is highly prevalent in human cancer and has been actively pursued as a target for drug discovery. Much progress has been made in drugging KRAS G12C, owing to the ability of inhibitors to covalently target its oncogenic cysteine mutation at codon 12. A number of KRAS G12C inhibitors have advanced to clinical development and are being investigated for the treatment of a variety of solid tumors. Notably,...

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PMID: 41769711
DOI: 10.1021/acs.jmedchem.5c02279

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KRAS

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Discovery and Optimization of a Potent, Efficacious, and Brain-Penetrant Inhibitor of KRAS G12C.PMID 41769711Read ↗

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