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| 25mg |
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Purity: ≥98%
Enasidenib mesylate (formerly known as AG-221; CC-90007; AG221; CC90007; trade name Idhifa), the mesylate salt of enasidenib, is a first-in-class, oral, potent and selective IDH2 (Isocitrate dehydrogenase 2) inhibitor approved in 2017 for the treatment of 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 concurrently with inducing differentiation and impairing IDH2-mutant leukemia cells' ability to self-renew. Leukemic cells undergo differentiation when treated with enasidenib (AG-221); at two weeks, the peripheral blood's CD11b+ population rises while the c-Kit+ population falls[2].
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| ln Vivo |
In a primary xenograft mouse model of IDH2-mutant acute myeloid leukemia (AML), treatment with enasidenib (AG-221) substantially increases survival[1]. Enasidenib (AG-221), a mutant IDH2 inhibitor, causes changes in self-renewal/differentiation in an IDH2-mutant AML model in vivo and modifies the epigenetic state of IDH2-mutant cells. 2-HG is reduced in vivo by 96.7% when enosetinib (10 mg/kg or 100 mg/kg bid) compared to pre-treatment levels. Furthermore, treatment with ezetinib restores the development of megakaryocyte-erythroid progenitor (MEP), which is inhibited by the expression of mutant IDH2 (mean MEP% mean, 39% Veh versus 50% AG-221). The effects of mutant IDH2 are reversed by ezetinib therapy; a substantial decrease in DNA methylation is seen, with 180 genes exhibiting 20 or more hypomethylated differentially methylated cytosines (DMCs) after treatment. When mice engrafted with Mx1-Cre IDH2R140QFlt3ITD AML cells are treated with enasidenib (100 mg/kg bid), 2-hydroxyglutarate (2-HG) levels are significantly reduced, which is consistent with on target inhibition. Mutant IDH2-mediated 2-HG synthesis is inhibited by énasidenib[2].
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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 |
C20H21F6N7O4S
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| Molecular Weight |
569.48
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| CAS # |
1650550-25-6
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| Related CAS # |
Enasidenib;1446502-11-9
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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.OS(=O)(C)=O
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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: ≥ 2.5 mg/mL (4.39 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7560 mL | 8.7799 mL | 17.5599 mL | |
| 5 mM | 0.3512 mL | 1.7560 mL | 3.5120 mL | |
| 10 mM | 0.1756 mL | 0.8780 mL | 1.7560 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.
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