Enasidenib is an inhibitor of mutant isocitrate dehydrogenase 2 (IDH2; IC50 = 0.1 ?M for IDH2 R140Q).1 It is selective for IDH2 R140Q over wild-type IDH2, wild-type IDH1, and IDH1 R132H (IC50s = 1.8, 0.45, and 48.4 ?M, respectively). Enasidenib (0.1, 1, and 5 ?M) inhibits production of D-2-hydroxyglutarate and induces differentiation in primary acute myeloid leukemia (AML) cells expressing IDH2 R140Q. It increases survival in a patient-derived xenograft (PDX) mouse model when administered at doses of 5, 15, and 45 mg/kg. Formulations containing enasidenib have been used in the treatment of AML.
1.Yen, K., Travins, J., Wang, F., et al.AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutationsCancer Discov.7(5)478-493(2017)