Enasidenib mesylate

SKU: orb1703967

Description

Enasidenib mesylate

Research Area

Metabolism Research

Key Properties

• CAS Number: 1650550-25-6
• MW: 569.48
• Purity: 99.86%
• Formula: C₂₀H₂₁F₆N₇O₄S
• SMILES: CS(O)(=O)=O.CC(C)(O)CNc1nc(Nc2ccnc(c2)C(F)(F)F)nc(n1)-c1cccc(n1)C(F)(F)F
• Target: Isocitrate Dehydrogenase (IDH),Dehydrogenase
• Solubility: DMSO:80 mg/mL (140.48 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (5.79 mM)

Bioactivity

• In Vivo:
  In an IDH2-mutant acute myeloid leukemia (AML) primary xenograft mouse model, treatment with Enasidenib mesylate (AG-221) significantly improves survival. Acting as a mutant IDH2 inhibitor, enasidenib remodels the epigenetic state of IDH2-mutant cells, inducing alterations in self-renewal/differentiation in an IDH2-mutant AML model in vivo. Enasidenib mesylate treatment at doses of 10 mg/kg or 100 mg/kg bid results in a substantial reduction in 2-HG levels in vivo, reaching 96.7% below pre-treatment levels.Furthermore, Enasidenib mesylate treatment restores megakaryocyte-erythroid progenitor (MEP) differentiation, which is suppressed by mutant IDH2 expression, as indicated by a mean MEP% increase from 39% in the vehicle group to 50% in the AG-221 group. The therapy also reverses the effects of mutant IDH2 on DNA methylation, with a significant reduction observed in DNA methylation, affecting 180 genes with 20 or more hypomethylated differentially methylated cytosines (DMCs) following treatment.Enasidenib mesylate therapy, particularly at a dose of 100 mg/kg bid, applied to mice engrafted with Mx1-Cre IDH2R140QFlt3ITD AML cells, markedly reduces 2-hydroxyglutarate (2-HG) levels, consistent with on-target inhibition. Enasidenib effectively inhibits the production of 2-HG mediated by mutant IDH2.
• In Vitro:
  Reversing the effects of mutant IDH2 on DNA methylation in mutant stem/progenitor cells, Enasidenib mesylate (AG-221) induces differentiation and impairs self-renewal of IDH2-mutant leukemia cells. Simultaneous inhibition of Flt3ITD further enhances these effects. In the context of Enasidenib mesylate (AG-221) therapy, leukemic cells undergo differentiation, resulting in an increased CD11b+ population and a decreased c-Kit+ population in the peripheral blood at 2 weeks.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AG 221 mesylate, AG 221 Mesylate, AG221 mesylate, AG221 Mesylate, AG-221 Mesylate, AG-221 mesylate, IDH2, Enasidenib mesylate, Enasidenib Mesylate

Compound Identifiers

PubChem CID

90480031