Published March 01, 2023 13:21
The G12C mutant KRas is considered druggable by covalent inhibitors. We have screened a covalent electrophilic fragment library (diverse non-covalent scaffolds with 40 different electrophilic functionalities) to identify suitable lead molecules targeting Cys12. The screening was based on Ellman's free thiol, protein NMR and cell viability assays. Two potential inhibitor chemotypes were identified.
Our results are published in the European Journal of Medicinal Chemistry.