Lim, Sang Min Westover, Kenneth D. Ficarro, Scott B. Harrison, Rane A. Choi, Hwan Geun Pacold, Michael E. Carrasco, Martin Hunter, John Kim, Nam Doo Xie, Ting Sim, Taebo Jaenne, Pasi A. Meyerson, Matthew Marto, Jarrod A. Engen, John R. Gray, Nathanael S. 2024-01-20T10:33:55Z 2024-01-20T10:33:55Z 2021-09-05 2014-01-03 1433-7851 https://pubs.kist.re.kr/handle/201004/127232 We report the synthesis of a GDP analogue, SML-8-73-1, and a prodrug derivative, SML-10-70-1, which are selective, direct-acting covalent inhibitors of the K-Ras G12C mutant relative to wild-type Ras. Biochemical and biophysical measurements suggest that modification of K-Ras with SML-8-73-1 renders the protein in an inactive state. These first-in-class covalent K-Ras inhibitors demonstrate that irreversible targeting of the K-Ras guanine-nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling. English John Wiley & Sons Ltd. SIGNAL-TRANSDUCTION CANCER MUTATIONS DOMAIN SWITCH Therapeutic Targeting of Oncogenic K-Ras by a Covalent Catalytic Site Inhibitor Article 10.1002/anie.201307387 1 Angewandte Chemie International Edition, v.53, no.1, pp.199 - 204 Angewandte Chemie International Edition 53 1 199 204 scie scopus 000328714900026 2-s2.0-84890947640 Chemistry, Multidisciplinary Chemistry Article SIGNAL-TRANSDUCTION CANCER MUTATIONS DOMAIN SWITCH cancer covalent inhibitors drug design K-Ras