Enasidenib is an oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes, with IC50s of 100 and 400 nM against IDH2 and IDH2, respectively.
IC50&Target
IC50: 100 nM (IDH2), 400 nM (IDH2)
体外研究
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 Flt3. 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 2wks.
体内研究
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 (10mg/kg or 100mg/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 (100mg/kg bid) treatment of mice engrafted with Mx1-Cre IDH2Flt3 AML cells markedly reduces 2-hydroxyglutarate (2-HG) levels consistent with on target inhibition. Enasidenib inhibits mutant IDH2-mediated 2-HG production.
分子式
C19H17F6N7O
分子量
473.38
CAS号
1446502-11-9
中文名称
恩西地平
运输条件
Room temperature in continental US; may vary elsewhere.