- Epacadostat
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- $39.00 / 5mg
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2026-03-13
- CAS:1204669-58-8
- Min. Order:
- Purity: 99.74%
- Supply Ability: 10g
- INCB-24360;INCB24360
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- $15.00 / 1KG
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2021-07-13
- CAS:1204669-58-8
- Min. Order: 1KG
- Purity: 99%+ HPLC
- Supply Ability: Monthly supply of 1 ton
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| | Epacadostat (INCB024360) Basic information |
| Product Name: | Epacadostat (INCB024360) | | Synonyms: | (Z)-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-((2-(sulfamoylamino)ethyl)amino)-1,2,5-oxadiazole-3-carboximidamide;Epacadostat (INCB24360, INCB024360);N-(3-Bromo-4-fluoro-phenyl)-N'-hydroxy-4-[2-(sulfamoylamino)ethylamino]-1,2,5-oxadiazole-3-carboxamidine;INCN024360;(Z)-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-[2-(sulfamoylamino)ethylamino]-1,2,5-oxadiazole-3-carboxamidine;Epacadostat(INCN024360);INCB-24360(INCB-024360);Epacadostat(INCB024360) | | CAS: | 1204669-58-8 | | MF: | C11H13BrFN7O4S | | MW: | 438.23 | | EINECS: | | | Product Categories: | | | Mol File: | 1204669-58-8.mol |  |
| | Epacadostat (INCB024360) Chemical Properties |
| Melting point | 159 - 161°C | | Boiling point | 700.9±70.0 °C(Predicted) | | density | 2.01±0.1 g/cm3(Predicted) | | storage temp. | -20°C | | solubility | Soluble in DMSO (up to at least 25 mg/ml) | | form | solid | | pka | 7.65±0.69(Predicted) | | color | White | | Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | | InChI | InChI=1S/C11H13BrFN7O4S/c12-7-5-6(1-2-8(7)13)17-11(18-21)9-10(20-24-19-9)15-3-4-16-25(14,22)23/h1-2,5,16,21H,3-4H2,(H,15,20)(H,17,18)(H2,14,22,23) | | InChIKey | FBKMWOJEPMPVTQ-UHFFFAOYSA-N | | SMILES | C(/C1=NON=C1NCCNS(=O)(=O)N)(=N\O)\NC1C=C(Br)C(F)=CC=1 |
| | Epacadostat (INCB024360) Usage And Synthesis |
| Description | Epacadostat is an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1) with an IC50 value of 7.1 nM in HeLa cells that demonstrates little activity against the related enzymes IDO2 or tryptophan 2,3-dioxygenase (TDO). It has been shown to promote T and natural killer-cell growth, to increase IFN-γ production, and to reduce conversion to regulatory T (Treg)-like cells in a coculture system of human allogeneic lymphocytes with either dendritic cells or tumor cells. Epacadostat can also inhibit tumor growth in tumor-bearing mice in a lymphocyte-dependent manner. | | Uses | Epacadostat is a potent and novel indoleamine 2,3-dioxygenase (IDO1) inhibitor with IC50 of 10 nM. It has high selectivity over IDO2 and tryptophan 2,3-dioxygenase (TDO). | | Synthesis | GENERAL STEPS: To a 20 L glass reactor was added N-[2-(4-[4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-ylamino)ethyl]sulfonamide (799.4 g, 1.72 mol) and tetrahydrofuran (3.2 L). The resulting solution was stirred at 20 °C for 7 min. Water (1.6 L) was then added. The reaction mixture was cooled to 2 °C and 30 wt% sodium hydroxide solution (475 mL, 666.4 g, 4.99 mol, 2.9 eq.) was added slowly over 8 min. The reaction mixture was warmed to 20 °C and kept at this temperature for 16 hours. Next, methyl tert-butyl ether (8.0 L) was added to the reaction mixture over 23 minutes. After addition of water (2.7 L), the reaction mixture was cooled to about 0°C. Subsequently, 85 wt% phosphoric acid (370.7 g, 3.22 mol, 1.9 eq.) was slowly added over 9 min. The reaction mixture was warmed to 20 °C and stirred for 1 hour. After standing and stratifying, the phases were separated. The organic phase was retained in the reactor and water (2.9 L) and 85 wt% phosphoric acid (370.7 g, 3.22 mol) were added and stirred at 20 °C for 1 hour. Layering was again allowed to stand and the phases were separated. The organic phase was retained in the reactor and water (3.2 L) was added and stirred at 20 °C for 1 hour. Leave to stratify and separate the phases. The organic phase was retained in the reactor and distilled under reduced pressure at 20 °C to remove 3.4 kg of distillate. Ethanol (4.8 L) was added to the residue and the mixture was distilled to a volume of 3.2 L. This distillation process was repeated once. Ethanol (0.6 L) was added to adjust the volume to 4 L. The reaction mixture was stirred at 20 °C for 16 h. Water (6.39 L) was subsequently added. The resulting slurry was stirred for 5 h at 20 °C. The product was collected by filtration and washed twice with a mixture of ethanol (529 mL) and water (1059 mL). The product was dried under reduced pressure at 45 °C for 65 h to afford the target compound (719.6 g, 95.4%) as a white solid.1H NMR (400 MHz, DMSO-d6): δ 11.51 (s, 1H), 8.90 (s, 1H), 7.17 (t, J = 8.8 Hz, 1H), 7.11 (dd, J = 6.1, 2.7 Hz, 1H), 6.76 (m, 1H), 6.71 (t, J = 6.0 Hz, 1H), 6.59 (s, 2H), 6.23 (t, J = 6.1 Hz, 1H), 3.35 (dd, J = 10.9, 7.0 Hz, 2H), 3.10 (dd, J = 12.1, 6.2 Hz, 2H); C11H13BrFN7O4S ( MW 438.23), LCMS (EI) m/e 437.9/439.9 (M+ + H). | | in vivo | Female Balb/c mice bearing CT26 tumors are treated orally twice daily for 12 d with Epacadostat at 100 mg/kg. Epacadostat (INCB 024360) suppresses kynurenine equivalently in plasma, tumors, and lymph nodes. In na ve C57BL/6 mice, 50 mg/kg Epacadostat (INCB 024360) decreases plasma kynurenine levels within 1 hour and those levels stay at least 50% suppressed through the 8-hour time course[2]. | | target | IDO1 | | IC 50 | IDO1: 71.8 nM (IC50) | | References | [1] XIANGDONG LIU. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity.[J]. Blood, 2010: 3520-3530. DOI:10.1182/blood-2009-09-246124
[2] HOLLY K KOBLISH. Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors.[J]. Molecular Cancer Therapeutics, 2010, 9 2: 489-498. DOI:10.1158/1535-7163.mct-09-0628
[3] CAROLINE JOCHEMS. The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells.[J]. Oncotarget, 2016: 37762-37772. DOI:10.18632/oncotarget.9326
[4] SARAH YENTZ David S. Indoleamine 2,3-Dioxygenase (IDO) Inhibition as a Strategy to Augment Cancer Immunotherapy.[J]. BioDrugs, 2018, 32 4: 311-317. DOI:10.1007/s40259-018-0291-4
[5] MAYANNE M T ZHU Torsten O N Amanda R Dancsok. Indoleamine Dioxygenase Inhibitors: Clinical Rationale and Current Development.[J]. Current Oncology Reports, 2019, 21 1: 2. DOI:10.1007/s11912-019-0750-1
[6] TARA C MITCHELL. Epacadostat Plus Pembrolizumab in Patients With Advanced Solid Tumors: Phase I Results From a Multicenter, Open-Label Phase I/II Trial (ECHO-202/KEYNOTE-037).[J]. Journal of Clinical Oncology, 2018, 36 32: 3223-3230. DOI:10.1200/jco.2018.78.9602 |
| | Epacadostat (INCB024360) Preparation Products And Raw materials |
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