Article
Structure-based discovery of IHMT-IDH1-053 as a potent irreversible IDH1 mutant selective inhibitor.
European journal of medicinal chemistry - 5 Aug 2023
Liang Qianmao, Wang Beilei, Zou Fengming, Guo Gongrui, Wang Wenliang, Wang Wei, Liu Qingwang, Shen Lijuan, Hu Chen, Wang Wenchao, Wang Aoli, Huang Tao, He Yuying, Xia Ruixiang, Ge Jian, Liu Jing, Liu Qingsong
Abstract excerpt
Through a structure-based irreversible drug design approach, we have discovered a highly potent IDH1-mutant inhibitor compound 16 (IHMT-IDH1-053) (IC50 = 4.7 nM), which displays high selectivity against IDH1 mutants over IDH1 wt and IDH2 wt/mutants. The crystal structure demonstrates that 16 binds to the IDH1 R132H protein in the allosteric pocket adjacent to the NAPDH binding pocket through a covalent bond with...
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