Enasidenib是口服具有活力的、可逆的、选择性IDH2突变酶抑制剂，抑制IDH2R140Q和 IDH2R172K的IC50分别为100 和 400 nM。

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

The compound has been demonstrated to reduce 2-HG levels by >90% and reverse histone and deoxyribonucleic acid (DNA) hypermethylation in vitro, and to induce differentiation in leukemia cell models[2].

AG-221 is able to potently reduce 2HG found in the bone marrow, plasma and urine of engrafted mice. Treatment also induced a dose dependent, statistically significant, survival benefit. A proliferative burst of the human specific CD45+ blast cells is followed by cellular differentiation as measured by the expression of CD11b, CD14 and CD15 and cell morphology after AG-221 treatment[2]. AG-221 treatment also restores megakaryocyte-erythroid progenitor (MEP) differentiation that is suppressed by mutant IDH2 expression and reverses the effects of mutant IDH2 on DNA methylation in mutant stem/progenitor cells. Clinicalal trials combining IDH2 inhibitors with other targeted AML therapies are warranted in order to increase therapeutic efficacy[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.

1446502-11-9

C19H17F6N7O

473.383

恩西地平;AG-221

H2O:<1 mgml
Ethanol:100 mg/mL (211.25 mM)
DMSO:10 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years