Enasidenib mesylate

Research use only, not for human use.

Enasidenib mesylate (AG-221 mesylate) is a potent and selective IDH2 mutase inhibitor that promotes differentiation of leukemia myeloid cells for the treatment of acute myeloid leukemia.

Enasidenib mesylate is a first-in-class, oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes.

Enasidenib (AG-221) reverses the effects of mutant IDH2 on DNA methylation in mutant stem/progenitor cells. Enasidenib induces differentiation and impairs self-renewal of IDH2-mutant leukemia cells, effects that are further enhanced by simultaneous inhibition of Flt3ITD. Enasidenib (AG-221) therapy induces differentiation of leukemic cells, with an increase in the CD11b+ population and a decrease in the c-Kit+ population in the peripheral blood at 2 wks.

Treatment with enasidenib (AG-221) significantly improves survival in an IDH2-mutant acute myeloid leukemia (AML) primary xenograft mouse model. Enasidenib (AG-221), a mutant IDH2 inhibitor, remodels the epigenetic state of IDH2-mutant cells and induces alterations in self-renewal/differentiation in IDH2-mutant AML model in vivo. Enasidenib treatment (10 mg/kg or 100 mg/kg bid) leads to a reduction in 2-HG in vivo (96.7% below pre-treatment levels). Moreover, Enasidenib treatment restores megakaryocyte-erythroid progenitor (MEP) differentiation that is suppressed by mutant IDH2 expression (mean MEP% mean, 39% Veh vs 50% AG-221). Enasidenib therapy reverses the effects of mutant IDH2; a significant reduction is observed in DNA methylation, including 180 genes that have 20 or more hypomethylated differentially methylated cytosines (DMCs) following treatment. Enasidenib (100 mg/kg bid) treatment of mice engrafted with Mx1-Cre IDH2R140QFlt3ITD AML cells markedly reduces 2-hydroxyglutarate (2-HG) levels consistent with on target inhibition. Enasidenib inhibits mutant IDH2-mediated 2-HG production.

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Metabolic Enzyme/Protease

Dehydrogenase

Dehydrogenase

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1650550-25-6

569.48

C20H21F6N7O4S

>98% (HPLC)

In Vitro:?DMSO : ≥ 100 mg/mL (175.60 mM)

CS(O)(=O)=O.CC(C)(O)CNc1nc(Nc2ccnc(c2)C(F)(F)F)nc(n1)-c1cccc(n1)C(F)(F)F

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(-20℃)

With Ice Pack

≥ 2 years