1446502-11-9
1446502-11-9 structure
- Name: Enasidenib
- Chemical Name: Enasidenib
- CAS Number: 1446502-11-9
- Molecular Formula: C19H17F6N7O
- Molecular Weight: 473.375
- Catalog: Signaling Pathways Metabolic Enzyme/Protease Isocitrate Dehydrogenase (IDH)
- Create Date: 2018-09-09 10:52:00
- Modify Date: 2024-01-02 18:47:27
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Enasidenib is an oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes, with IC50s of 100 and 400 nM against IDH2R140Q and IDH2R172K, respectively.
| Name | Enasidenib |
|---|---|
| Synonyms |
AG-221
2-Methyl-1-[(4-[6-(trifluoromethyl)-2-pyridinyl]-6-{[2-(trifluoromethyl)-4-pyridinyl]amino}-1,3,5-triazin-2-yl)amino]-2-propanol 2-Methyl-1-(4-(6-(trifluoromethyl)pyridin-2-yl)-6-(2-(trifluoromethyl)pyridin-4-ylamino)-1,3,5-triazin-2-ylamino)propan-2-ol CC-90007 Enasidenib UNII:3T1SS4E7AG 2-Propanol, 2-methyl-1-[[4-[6-(trifluoromethyl)-2-pyridinyl]-6-[[2-(trifluoromethyl)-4-pyridinyl]amino]-1,3,5-triazin-2-yl]amino]- |
| Description | Enasidenib is an oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes, with IC50s of 100 and 400 nM against IDH2R140Q and IDH2R172K, respectively. |
|---|---|
| Related Catalog | |
| Target |
IC50: 100 nM (IDH2R140Q), 400 nM (IDH2R172K)[1] |
| 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[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 (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[2]. |
| References |
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Boiling Point | 581.0±60.0 °C at 760 mmHg |
| Molecular Formula | C19H17F6N7O |
| Molecular Weight | 473.375 |
| Flash Point | 305.2±32.9 °C |
| Exact Mass | 473.139862 |
| PSA | 108.74000 |
| LogP | 4.24 |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C |
| Index of Refraction | 1.573 |
| Storage condition | -20℃ |