AG-221 free base · Synonyms: Enasidenib

Enasidenib is an oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes.

For research use only. Not for human or veterinary use.

Target Isocitrate Dehydrogenase (IDH)

Research area Cancer

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Data Sheet SDS COA

AG-221 structure

CAS No.: 1446502-11-9

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
1 g	USD 380.00	BP-02477-1g	In stock	Get quote
2 g	USD 608.00	BP-02477-2g	In stock	Get quote
3 g	USD 730.00	BP-02477-3g	In stock	Get quote
5 g	USD 972.00	BP-02477-5g	In stock	Get quote
10 g	USD 1,550.00	BP-02477-10g	In stock	Get quote
25 g	USD 3,110.00	—	In stock	Get quote

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Description

Enasidenib is an oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes, with IC50s of 100 and 400 nM against IDH2 R140Q and IDH2 R172K, respectively.

Biological activity

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[1]. 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.

Identifiers

SMILES: CC(C)(O)CNC1=NC(=NC(NC2=CC(=NC=C2)C(F)(F)F)=N1)C1=NC(=CC=C1)C(F)(F)F
InChIKey: DYLUUSLLRIQKOE-UHFFFAOYSA-N

Specifications

MW (average): 473.3750
Formula: C₁₉H₁₇F₆N₇O
CAS No.: 1446502-11-9
Physical state: Solid
Color: White to off-white
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20°C, 3 years , 4°C, 2 years ; In solvent -20°C, 6 months;

Solubility

Soluble in DMSO

Documents

References

[1].Exploring the Pathway: IDH Mutations and Metabolic Dysregulation in Cancer Cells: A Novel Therapeutic Target. MAY 29, 2015

[2].Alan H. Shih, et al. AG-221, a Small Molecule 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. Blood 2014 124:437.

Same target

Search Isocitrate Dehydrogenase (IDH)

Same research area

Search Cancer