Article
KRAS is vulnerable to reversible switch-II pocket engagement in cells.
Nature chemical biology - 1 Jun 2022
Vasta James D, Peacock D Matthew, Zheng Qinheng, Walker Joel A, Zhang Ziyang, Zimprich Chad A, Thomas Morgan R, Beck Michael T, Binkowski Brock F, Corona Cesear R, Robers Matthew B, Shokat Kevan M
Abstract excerpt
Current small-molecule inhibitors of KRAS(G12C) bind irreversibly in the switch-II pocket (SII-P), exploiting the strong nucleophilicity of the acquired cysteine as well as the preponderance of the GDP-bound form of this mutant. Nevertheless, many oncogenic KRAS mutants lack these two features, and it remains unknown whether targeting the SII-P is a practical therapeutic approach for KRAS mutants beyond G12C....
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