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Ref Type Journal Article
PMID (24259466)
Authors Lim SM, Westover KD, Ficarro SB, Harrison RA, Choi HG, Pacold ME, Carrasco M, Hunter J, Kim ND, Xie T, Sim T, Janne PA, Meyerson M, Marto JA, Engen JR, Gray NS
Title Therapeutic targeting of oncogenic K-Ras by a covalent catalytic site inhibitor.
Journal Vol Issue Date Pages Journal Short Title
Angewandte Chemie (International ed. in English) 53 1 2014 Jan 3 199-204 Angew Chem Int Ed Engl
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
SML-10-70-1 SML-10-70-1 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
SML-10-70-1 SML-10701|SML-10 70 1|SML10701|SML 10701 KRAS G12C inhibitor 33 SML-10-70-1 is an SML-8-73-1 prodrug and GTP-competitive inhibitor of KRAS G12C capable of passing through cell membranes (PMID: 24259466).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References