Targets of Enasidenib

Enasidenib (Enasidenib) is a small molecule inhibitor of isocitrate dehydrogenase 2 (IDH2) enzyme. Etanacitinib targets mutant IDH2 variants R140Q, R172S, and R172K in vitro at approximately 40-fold lower concentrations than the wild-type enzyme. In a mouse xenograft model of IDH2-mutant acute myeloid leukemia, inhibition of the mutant IDH2 enzyme by enacinib resulted in reduced 2-hydroxyglutarate (2-HG) levels and induction of myeloid differentiation in vitro and in vivo. In blood samples from acute myeloid leukemia patients with mutated IDH2, ensidipine reduced 2-HG levels, reduced osteoblast counts, and increased the percentage of mature myeloid cells.