Isocitrate Dehydrogenase (IDH)

Crelosidenib (gentisate) is a selective oral inhibitor of mutant isocitrate dehydrogenase (IDH) enzymes, specifically targeting IDH1 R132H (IC50 of 6.27 nM), IDH1 R132C (IC50 of 3.71 nM), IDH2 R140Q (IC50 of 36.9 nM), and IDH2 R172K (IC50 of 11.5 nM). It demonstrates decreased activity against wild-type IDH enzymes. Crelosidenib is primarily utilized in research focusing on metabolic dysregulation and oncogenic pathways associated with IDH mutations in various cancers.

AGI-12026 is a brain-penetrant dual inhibitor targeting mutant isocitrate dehydrogenase 1 and 2 (IDH1/2). It acts as an allosteric modulator, demonstrating partial inhibition of the IDH1-R132H homodimer. This compound is suitable for research applications related to glioma and provides a valuable tool for studying the role of mutant IDH enzymes in cancer biology.

Enasidenib mesylate is a selective inhibitor of mutant isocitrate dehydrogenase 2 (IDH2) enzymes, demonstrating potent and reversible binding. It primarily exerts its biological activity by altering the metabolism of 2-hydroxyglutarate, thus affecting cellular processes associated with cancer progression. This compound is utilized in research focused on hematologic malignancies, particularly those driven by IDH2 mutations.