Enasidenib (AG-221) is an orally available inhibitor of specific mutant forms of the mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2), with potential antineoplastic activity.

IDH2 (R172K):400 nM, IDH2 (R140Q):100nM

该化合物经验证可将2-HG水平降低超过90%，并在体外逆转组蛋白和脱氧核糖核酸(DNA)的高甲基化，同时在白血病细胞模型中诱导分化[2]。

Enasidenib能有效减少移植小鼠骨髓、血浆和尿液中的2HG含量。Enasidenib治疗能恢复由突变IDH2表达抑制的巨核细胞-红系前体（MEP）分化，并可逆转突变IDH2在突变干/前体细胞中对DNA甲基化的影响。因此，结合IDH2抑制剂和其他针对AML（急性髓性白血病）的靶向治疗进行临床试验，以提高治疗效果是有必要的[1]。

Untranslated region-mediated luciferase reporter expression: HEK293 cells are transfected with a GEMS reporter vector that contains the luciferase open-reading frame flanked by and under post-transcriptional control of the BMI-1 5′ and 3′ UTRs. The resulting stable cells (F8) are treated with PTC-209 or vehicle control overnight, and then luciferase reporter activity is determined using Bright-Glo assays. The assays are run in triplicate for each point, and the percentage of inhibition was calculated against vehicle control.