Enasidenib

Research use only, not for human use.

An orally available, selective, potent inhibitor of mutant IDH2 with IC50s of 100-400 nM for IDH2R140Q homodimer.

An orally available, selective, potent inhibitor of mutant IDH2 with IC50s of 100-400 nM for IDH2R140Q homodimer, IDH2R172K homodimer and IDH2WT/R140Q, IDH2WT/R172K; less potent for IDH2WT homodimer and IDH1WT homodimer; suppresses 2HG production and induces cellular differentiation in primary human IDH2 mutation-positive AML cells ex vivo and in xenograft mouse models.Blood Cancer Approved(In Vitro):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 2wks.(In Vivo):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 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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AG-221 | CC-90007

Metabolic Enzyme/Protease

IDH

IDH2

Cancer

Blood cancer

1446502-11-9

473.375

C19H17F6N7O

>98% (HPLC)

10 mM in DMSO

CC(C)(CNC1=NC(=NC(=N1)C2=NC(=CC=C2)C(F)(F)F)NC3=CC(=NC=C3)C(F)(F)F)O

2-Propanol, 2-methyl-1-[[4-[6-(trifluoromethyl)-2-pyridinyl]-6-[[2-(trifluoromethyl)-4-pyridinyl]amino]-1,3,5-triazin-2-yl]amino]-

(-20℃)

With Ice Pack

≥ 2 years