Identification of mIDH1 R132C/S280F Inhibitors from Natural Products by Integrated Molecular Docking, Pharmacophore Modeling and Molecular Dynamics Simulations.

ABSTRACT: Mutant isocitrate dehydrogenase 1 (mIDH1) is a common driving factor in acute myeloid leukemia (AML), with the R132 mutation accounting for a high proportion. The U.S. Food and Drug Administration (FDA) approved Ivosidenib, a molecular entity that targets IDH1 with R132 mutations, as a promising therapeutic option for AML with mIDH1 in 2018. It was of concern that the occurrence of disease resistance or recurrence, attributed to the IDH1 R132C/S280F second site mutation, was observed in certain patients treated with Ivosidenib within the same year. Furthermore, it should be noted that most mIDH1 inhibitors demonstrated limited efficacy against mutations at this specific site. Therefore, there is an urgent need to investigate novel inhibitors targeting mIDH1 for combating resistance caused

SUBMITTER: Zhang W 

PROVIDER: S-EPMC10976062 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature