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Enasidenib mesylate

Names

[ CAS No. ]:
1650550-25-6

[ Name ]:
Enasidenib mesylate

[Synonym ]:
Enasidenib mesylate
AG-221 mesylate
UF6PC17XAV
CC-90007
2-Methyl-1-[(4-[6-(trifluoromethyl)-2-pyridinyl]-6-{[2-(trifluoromethyl)-4-pyridinyl]amino}-1,3,5-triazin-2-yl)amino]-2-propanol methanesulfonate (1:1)
2-Propanol, 2-methyl-1-[[4-[6-(trifluoromethyl)-2-pyridinyl]-6-[[2-(trifluoromethyl)-4-pyridinyl]amino]-1,3,5-triazin-2-yl]amino]-, methanesulfonate (1:1) (salt)
UNII:UF6PC17XAV
Enasidenib (mesylate)

Biological Activity

[Description]:

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

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Isocitrate Dehydrogenase (IDH)
Research Areas >> Cancer

[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 2 wks[2].

[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 (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[2].

[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.


[Related Small Molecules]

AG-120 | Enasidenib | AGI-5198 | Vorasidenib (AG-881) | AGI-6780 | GSK864 | IDH-305 | BAY-1436032 | Mutant IDH1 inhibitor | Mutant IDH1-IN-1 | Mutant IDH1-IN-2 | Olutasidenib

Chemical & Physical Properties

[ Molecular Formula ]:
C20H21F6N7O4S

[ Molecular Weight ]:
569.481

[ Exact Mass ]:
569.127991

[ Storage condition ]:
2-8℃

Related Compounds