mutant-specific IDH1 inhibitor

Mutant-specific IDH1 inhibitors are a class of small molecule targeted therapies designed to selectively inhibit mutated forms of the isocitrate dehydrogenase 1 (IDH1) enzyme, most commonly the R132H substitution. In various cancers, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and gliomas, these mutations confer a neomorphic activity that catalyzes the reduction of alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (D2HG). Elevated D2HG levels competitively inhibit alpha-ketoglutarate-dependent dioxygenases, leading to DNA and histone hypermethylation and a subsequent block in cellular differentiation. By selectively binding to the mutant enzyme, these inhibitors reduce D2HG production, thereby reversing epigenetic dysregulation and inducing the differentiation of malignant cells. Several agents in this class, such as ivosidenib and olutasidenib, have gained regulatory approval for hematologic and solid tumor indications.

Other names

mutant IDH1 inhibitormIDH1 inhibitormIDH-1 inhibitormIDH 1 inhibitormutant-selective IDH1 inhibitor