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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
Enasidenib (formerly AG221; CC90007; AG-221; CC-90007; Idhifa) is an orally bioactive, first-in-class, and selective inhibitor of IDH2 (Isocitrate dehydrogenase 2) with potential anticancer activity. As of 2017, it has been approved to treat relapsed or refractory acute myeloid leukemia in people with specific mutations of the IDH2 gene, determined by an FDA-approved IDH2 companion diagnostic test. It inhibits IDH2R140Q and IDH2R172K with IC50s of 100 and 400 nM, respectively.
ln Vitro |
In mutant stem/progenitor cells, enasidenib (AG-221) counteracts the effects of mutant IDH2 on DNA methylation. Enasidenib inhibits Flt3ITD, which further amplifies the effect of inducing differentiation and impairing IDH2 mutant leukemia cells' ability to self-renew. Treatment with enasidenib (AG-221) causes leukemic cell differentiation after two weeks [2].
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ln Vivo |
In an IDH2-mutant acute myeloid leukemia (AML) primary xenograft mouse model, enasidenib (AG-221) treatment markedly increases survival [1]. Mutant IDH2 inhibitor enasidenib (AG-221) alters the epigenetic state of IDH2 mutant cells and causes self-renewal/differentiation alterations in IDH2 mutant AML models in vivo. Treatment with enasidenib (10 mg/kg or 100 mg/kg bid) reduced 2-HG in vivo by 96.7% compared to pre-treatment levels. Moreover, the administration of enasidenib remedied the inhibition of mutant IDH2 expression on megakaryocyte-erythroid progenitor (MEP) differentiation (mean MEP% mean, 39% Veh vs. 50% AG-221). The effects of mutant IDH2 were reversed by ezetinib treatment; notable reductions in DNA methylation were noted, with 180 genes exhibiting 20 or more hypomethylated differentially methylated cytosines (DMCs) following treatment. 2-hydroxyglutarate (2-HG) levels were markedly decreased in mice implanted with Mx1-Cre IDH2R140QFlt3ITD AML cells after receiving ensesidenib (100 mg/kg bid), in line with target inhibition. Mutant IDH2-mediated 2-HG production is inhibited by enosenib [2].
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Animal Protocol |
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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. |
Molecular Formula |
C19H17F6N7O
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Molecular Weight |
473.38
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CAS # |
1446502-11-9
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Related CAS # |
Enasidenib mesylate;1650550-25-6;Enasidenib-d6;2095569-76-7
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SMILES |
CC(O)(C)CNC1=NC(C2=NC(C(F)(F)F)=CC=C2)=NC(NC3=CC(C(F)(F)F)=NC=C3)=N1
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Synonyms |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.39 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (2.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.1125 mL | 10.5623 mL | 21.1247 mL | |
5 mM | 0.4225 mL | 2.1125 mL | 4.2249 mL | |
10 mM | 0.2112 mL | 1.0562 mL | 2.1125 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.