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Medchemexpress/INCB 024360(Synonyms: Epacadostat)/HY-15689/100mg
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Medchemexpress/INCB 024360(Synonyms: Epacadostat)/HY-15689/100mg
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4000-520-616
INCB024360isapotentandselectiveIDO1inhibitorwithIC50of71.8nM±17.5nM.
Description

INCB024360isapotentandselectiveIDO1inhibitorwithIC50of71.8nM±17.5nM.

IC50&Target

IC50:71.8nM±17.5nM(IDO1),7.1nM±0.6nM(IDO1,inHeLacells)[1]

InVitro

Incellularassays,INCB024360(INCB024360)selectivelyinhibitshumanIDO1withIC50valuesofapproximately10nM,demonstratinglittleactivityagainstotherrelatedenzymessuchasIDO2ortryptophan2,3-dioxygenase(TDO).INCB024360alsoexhibitssignificantactivitytowardmouseIDO1,withanIC50valueof52.4nM±15.7nM,inasimilarassayusingmouseIDO1-transfectedHEK293/MSRcells[1].

InVivo

FemaleBalb/cmicebearingCT26tumorsaretreatedorallytwicedailyfor12dwithINCB024360(INCB024360)at100mg/kg.INCB024360suppresseskynurenineequivalentlyinplasma,tumors,andlymphnodes.InnaïveC57BL/6mice,50mg/kgINCB024360decreasesplasmakynureninelevelswithin1hourandthoselevelsstayatleast50%suppressedthroughthe8-hourtimecourse[2].

ClinicalTrial
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References
  • [1].LiuX,etal.SelectiveinhibitionofIDO1effectivelyregulatesmediatorsofantitumorimmunity.Blood.2010Apr29;115(17):3520-30.

    [2].KoblishHK,etal.Hydroxyamidineinhibitorsofindoleamine-2,3-dioxygenasepotentlysuppresssystemictryptophancatabolismandthegrowthofIDO-expressingtumors.MolCancerTher.2010Feb;9(2):489-98.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.2819mL11.4095mL22.8191mL
5mM0.4564mL2.2819mL4.5638mL
10mM0.2282mL1.1410mL2.2819mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[1]

INCB024360(INCB024360)isdissolvedinDMSOandstored,andthendilutedwithappropriatemediabeforeuse[1].

TodetermineINCB024360activityagainstIDOinrecombinantcells,HEK293/MSRcellsaretransientlytransfectedwithfull-lengthhumanormouseIDO1,ormouseIDO2CDNA,withTransit-293transfectionreagentorLipofectamine2000reagents.INCB024360atdifferentconcentrationsisaddedtotherecoveredtransfectedcellsseededat2×104cellsperwellina96-wellplate(200μL/well).Thecellsareincubatedfor2days,andkyninthesupernatantsismeasuredasdescribedintheHeLacellassay.Thetryptophan2,3-dioxygenase(TDO)assayisperformedsimilarlywithHEK293/MSRcellstransfectedwithahumanTDOexpressionvector[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdmiNISTration
[2]

INCB024360(INCB024360)ispreparedin40%N,N-Dimethylacetamide,60%propyleneglycol(Mice)[2].

Mice[2]
ThefemaleC57BL/6micearedosedorallywith50mg/kgINCB024360.C57BL/6wild-typeorIdo1-/--deficientmiceareadministeredasingleoraldoseofINCB024360,atwhichpointfoodisremovedfromthecagesuntilafterthe8-htimepoint.Atvarioustimepointsafterdosing,miceareeuthanizedandbloodiscollectedbycardiacpuncture.PlasmaisanalyzedforthepresenceofINCB023843,INCB024360,tryptophan,andkynurenineaccordingtothemethodsbelow.Dataareanalyzedusingone-wayANOVAwithDunnett"sposttestforstatisticalsignificance.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References
  • [1].LiuX,etal.SelectiveinhibitionofIDO1effectivelyregulatesmediatorsofantitumorimmunity.Blood.2010Apr29;115(17):3520-30.

    [2].KoblishHK,etal.Hydroxyamidineinhibitorsofindoleamine-2,3-dioxygenasepotentlysuppresssystemictryptophancatabolismandthegrowthofIDO-expressingtumors.MolCancerTher.2010Feb;9(2):489-98.

MolecularWeight

438.23

Formula

C₁₁H₁₃BrFN₇O₄S

CASNo.

1204669-58-8

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥31mg/mL

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

Purity:99.65%