Epacadostat-INCB-024360-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEEpacadostatCat.No.:HY-15689CASNo.:1204669-58-8Synonyms:INCB024360分⼦式:C₁₁H₁₃BrFN₇O₄S分⼦量:438.23作⽤靶点:Indoleamine2,3-Dioxygenase(IDO)作⽤通路:MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(228.19mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2819mL11.4095mL22.8191mL5mM0.4564mL2.2819mL4.5638mL10mM0.2282mL1.1410mL2.2819mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.70mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.70mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.70mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.62mg/mL(5.98mM);Clearsolution5.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.62mg/mL(5.98mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Epacadostat(INCB024360)⼀种有效，选择性的IDO1抑制剂，IC50为71.8nM。IC50&TargetIDO171.8nM(IC50)体外研究Incellularassays,Epacadostat(INCB024360)selectivelyinhibitshumanIDO1withIC50valuesofapproximately10nM,demonstratinglittleactivityagainstotherrelatedenzymessuchasIDO2ortryptophan2,3-dioxygenase(TDO).Epacadostat(INCB024360)alsoexhibitssignificantactivitytowardmouseIDO1,withanIC50valueof52.4nM±15.7nM,inasimilarassayusingmouseIDO1-transfectedHEK293/MSRcells[1].体内研究FemaleBalb/cmicebearingCT26tumorsaretreatedorallytwicedailyfor12dwithEpacadostatat100mg/kg.Epacadostat(INCB024360)suppresseskynurenineequivalentlyinplasma,tumors,andlymphnodes.InnaïveC57BL/6mice,50mg/kgEpacadostat(INCB024360)decreasesplasmakynureninelevelswithin1hourandthoselevelsstayatleast50%suppressedthroughthe8-hourtimecourse[2].PROTOCOLCellAssay[1]TodetermineEpacadostatactivityagainstIDOinrecombinantcells,HEK293/MSRcellsaretransientlytransfectedwithfull-lengthhumanormouseIDO1,ormouseIDO2cDNA,withTransit-293transfectionreagentorLipofectamine2000reagents.Epacadostat(INCB024360)atdifferentconcentrationsisaddedtotherecoveredtransfectedcellsseededat2×104cellsperwellina96-wellplate(200μL/well).Thecellsareincubatedfor2days,andkyninthesupernatantsismeasuredasdescribedintheHeLacellassay.Thetryptophan2,3-dioxygenase(TDO)assayisperformedsimilarlywithHEK293/MSRcellstransfectedwithahumanTDOexpressionvector[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]ThefemaleC57BL/6micearedosedorallywith50mg/kgEpacadostat.C57BL/6wild-typeorIdo1-/--deficientmiceareadministeredasingleoraldoseofEpacadostat(INCB024360),atwhichpointfoodisremovedfrom2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEthecagesuntilafterthe8-htimepoint.Atvarioustimepointsafterdosing,miceareeuthanizedandbloodiscollectedbycardiacpuncture.PlasmaisanalyzedforthepresenceofEpacadostat(INCB024360),tryptophan,andkynurenineaccordingtothemethodsbelow.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CancerDiscov.2022May10;candisc.0680.2021.•IntJBiolSci.2021Jan1;17(1):339-352.•BrJPharmacol.2018Jul;175(14):3034-3049.•OncoImmunology.2020Mar9;9(1):1730538.•EurJMedChem.29October2022,114860.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LiuX,etal.SelectiveinhibitionofIDO1effectivelyregulatesmediatorsofantitumorimmunity.Blood.2010Apr29;115(17):3520-30.[2].KoblishHK,etal.Hydroxyamidineinhibitorsofindoleamine-2,3-dioxygenasepotentlysuppresssystemictryptophancatabolismandthegrowthofIDO-expressingtumors.MolCancerTher.2010Feb;9(2):489-98.[3].FuR,etal.LW106,anovelindoleamine2,3-dioxygenase1inhibitor,suppressestumourprogressionbylimitingstroma-immunecrosstalkandcancerstemcellenrichmentintumourmicro-environment.BrJPharmacol.201