Are There Therapeutic Strategies Targeting 2-Hydroxyglutarate?
Given its role in cancer, targeting the production or action of 2HG has become a promising therapeutic strategy. Small molecule inhibitors of mutant IDH enzymes, such as ivosidenib (AG-120) for IDH1 mutations and enasidenib (AG-221) for IDH2 mutations, have been developed and approved for the treatment of IDH-mutant AML. These inhibitors reduce the levels of 2HG, potentially reversing the epigenetic modifications and restoring normal cellular differentiation.
