Epacadostat-INCB-024360-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEEpacadostatCat. No.: HY-15689CAS No.: 1204669-58-8Synonyms: INCB 024360分式: CHBrFNOS分量: 438.23作靶點(diǎn): Indoleamine 2,3-Dioxygenase (IDO)作通路: Metabolic Enzyme/Protease儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 mo

2、nth溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 31 mg/mL (70.74 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.2819 mL 11.4095 mL 22.8191 mL5 mM 0.4564 mL 2.2819 mL 4.5638 mL10 mM 0.2282 mL 1.1410 mL 2.2819 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) INCB 024360 (Epacados

3、tat) is dissolved freshly in sodium citrate buffer prior to each experiment3.BIOLOGICAL ACTIVITY物活性 Epacadostat (INCB 024360)種有效，選擇性的 IDO1 抑制劑， IC50 為 71.8 nM17.5 nM。IC50 & Target IDO11/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE71.8 nM (IC50)體外研究 In cellular assays, Epacadostat (INCB 024360) se

4、lectively inhibits human IDO1 with IC50 values ofapproximately 10 nM, demonstrating little activity against other related enzymes such as IDO2 or tryptophan2,3-dioxygenase (TDO). Epacadostat (INCB 024360) also exhibits significant activity toward mouse IDO1,with an IC50 value of 52.4 nM15.7 nM, in a

5、 similar assay using mouse IDO1-transfected HEK293/MSR cells1.體內(nèi)研究 Female Balb/c mice bearing CT26 tumors are treated orally twice daily for 12 d with Epacadostat at 100mg/kg. Epacadostat (INCB 024360) suppresses kynurenine equivalently in plasma, tumors, and lymphnodes. In nave C57BL/6 mice, 50 mg/

6、kg Epacadostat (INCB 024360) decreases plasma kynurenine levelswithin 1 hour and those levels stay at least 50% suppressed through the 8-hour time course 2.PROTOCOLCell Assay 1 To determine Epacadostat activity against IDO in recombinant cells, HEK293/MSR cells are transientlytransfected with full-l

7、ength human or mouse IDO1, or mouse IDO2 cDNA, with Transit-293 transfectionreagent or Lipofectamine 2000 reagents. Epacadostat (INCB 024360) at different concentrations is added tothe recovered transfected cells seeded at 2104 cells per well in a 96-well plate (200 L/well). The cells areincubated f

8、or 2 days, and kyn in the supernatants is measured as described in the HeLa cell assay. Thetryptophan 2,3-dioxygenase (TDO) assay is performed similarly with HEK293/MSR cells transfected with ahuman TDO expression vector 1.MCE has not independently confirmed the accuracy of these methods. They are f

9、or reference only.Animal Mice 2Administration 2 The female C57BL/6 mice are dosed orally with 50 mg/kg Epacadostat. C57BL/6 wild-type or Ido1-/-deficientmice are administered a single oral dose of Epacadostat (INCB 024360), at which point food is removed fromthe cages until after the 8-h time point.

10、 At various time points after dosing, mice are euthanized and blood iscollected by cardiac puncture. Plasma is analyzed for the presence of Epacadostat (INCB 024360),tryptophan, and kynurenine according to the methods below.MCE has not independently confirmed the accuracy of these methods. They are

11、for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Br J Pharmacol. 2018 Jul;175(14):3034-3049. Sci Rep. 2018 Apr 3;8(1):5488. Toxicol Appl Pharmacol. 2017 May 15;323:74-80. PLoS One. 2019 May 21;14(5):e0217276. Methods Mol Biol. 2018;1711:351-398.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Ma

12、ster of Small Molecules 您邊的抑制劑師www.MedChemE1. Liu X, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30.2. Koblish HK, et al. Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan cata

13、bolism and thegrowth of IDO-expressing tumors. Mol Cancer Ther. 2010 Feb;9(2):489-98.3. Fu R, et al. LW106, a novel indoleamine 2,3-dioxygenase 1 inhibitor, suppresses tumour progression by limiting stroma-immunecrosstalk and cancer stem cell enrichment in tumour micro-environment. Br J Pharmacol. 2018 Jul;175(14):3034-3049.McePdf