AG-221 (Enasidenib)

AG-221(Enasidenib) is a potent, selective, and reversible inhibitor of mutant IDH2 (isocitrate dehydrogenase type 2). It specifically inhibits IDH2 in the mitochondria, blocking the formation of oncometabolite 2-hydroxyglutarate (2HG). In in vitro studies, AG-221 reduces 2-HG levels by >90%, reverses histone and DNA hypermethylation, and induces cellular differentiation in leukemia cell models.