Discovery of novel IDH1-R132C inhibitors through structure-based virtual screening.

ABSTRACT: Isocitrate dehydrogenase (IDH) belongs to a family of enzymes involved in glycometabolism. It is found in many living organisms and is one of the most mutated metabolic enzymes. In the current study, we identified novel IDH1-R132C inhibitors using docking-based virtual screening and cellular inhibition assays. A total of 100 molecules with high docking scores were obtained from docking-based virtual screening. The cellular inhibition assay demonstrated five compounds at a concentration of 10 μM could inhibit cancer cells harboring the IDH1-R132C mutation proliferation by > 50%. The compound (T001-0657) showed the most potent effect against cancer cells harboring the IDH1-R132C mutation with a half-maximal inhibitory concentration (IC₅₀) value of 1.311

SUBMITTER: Hu C 

PROVIDER: S-EPMC9491111 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature