Belatacept-BMS-224818-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBelataceptCat.No.:HY-108813CASNo.:706808-37-9Synonyms:BMS224818;LEA29Y作⽤靶点:Others作⽤通路:Others储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Belatacept(BMS224818)⼀种选择性T细胞共刺激(T-cellcostimulation)阻滞剂。Belatacept与CD80/86配体结合⽽抑制CD-28介导的T细胞共刺激。Belatacept可⽤于器官移植免疫抑制的研究。IC50&TargetCD80/86[1]体外研究Belatacept(0-5mg/mL,1h)inhibitsT-cellproliferationinadose-dependentmanner[2].Belatacept(500ng/mL,7days)enhancespredominanceofeffector-memoryT-cellsafterallogeneicstimulation[2].Belatacept(100,500ng/mL,7days)hasnoeffectondifferentiationandallogeneicIFNγproductionofisolatedeffector-memoryTcells[2].Belatacept(10ꢀμg/mL,1h)doesnotinhibitfollicularTCell-dependentB-Celldifferentiation[4].Belatacept(40ꢀμg/mL,10days)reducesplasmablastdifferentiation,Igproduction,andthemajortranscriptionfactorBlimp-1inaTcell-independentmanner[5].Belatacept(40ꢀμg/mL,30min)inducesactivationoftheSTAT3transcriptionfactorinstimulatedBcellsandreducedtheexpressionofCD86[5].CellViabilityAssay[2]CellLine:PBMCsfromhealthyvolunteersConcentration:0-5mg/mLIncubationTime:1hResult:InhibitedT-cellproliferationlwithIC50valuesof215ng/mL,andresidualT-cell1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEproliferation(±30%)wasstillpresentathighdoses.WesternBlotAnalysis[5]CellLine:CD40LandIL-21stimulatedBcellsConcentration:40ꢀμg/mLIncubationTime:15,30minResult:IncreasedinSTATsignalingdeterminedbyincreasedSTAT3phosphorylation.体内研究Belatacept(intraperitonealinjection,60mg/kg)inhibitsABMR(Antibody-MediatedRejection),andinhibitsacuterejectionwhencombinedwithBTLA(BandTlymphocyteattenuator)overexpressiontherapy[3].Belatacept(intravenousinjection,20mg/kg)displaysimmunosuppressiveactivitiesinmonkeysimmunizedwithsheepredbloodcell[6].AnimalModel:Acuterejectionmodeloforthotopickidneytransplantationinrats[3]Dosage:60mg/kgAdministration:Intraperitonealinjection,atpostoperativeand4daysaftertransplantation.Result:Inhibitedcreatinineincreaseafterkidneytransplantation(combinedwithBTLAoverexpressiontherapy).ReducedC4dingraftIFstaining,andreducedCD138infiltrationandDSAproduction.AnimalModel:Rhesusmonkeysimmunizedwithsheepredbloodcell[6]Dosage:Intra-operatively10mg/kg,onday4(15mg/kg)andonpost-operativedays14,28,42,56,70(20mg/kg).Administration:intravenousinjectionResult:Causeda50%reductioninthepeakanti-SRBCresponse.Prolongedrenalallograftsurvivalandsynergieswithconventionalimmunosuppression.REFERENCES[1].GeorgeMelvin,etal.Belatacept:Aworthyalternativetocyclosporine?.JPharmacolPharmacother.2012Jan-Mar;3(1):90–92.[2].GretchenNdeGraav,etal.Down-RegulationofSurfaceCD28underBelataceptTreatment:AnEscapeMechanismforAntigen-ReactiveT-Cells.PLoSOne.2016Feb26;11(2):e0148604.[3].HengchengZhang,etal.CombinedImmunotherapyWithBelataceptandBTLAOverexpressionAttenuatesAcuteRejectionFollowingKidneyTransplantation.FrontImmunol.2021Feb24;12:618737.[4].GretchenNdeGraav,etal.BelataceptDoesNotInhibitFollicularTCell-DependentB-CellDifferentiationinKidneyTransplantation.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEFrontImmunol.2017May31;8:641.[5].laireLeibler,etal.ControlofHumoralResponseinRenalTransplantationbyBelataceptDependsonaDirectEffectonBCellsandImpairedTFollicularHelper-BCellCrosstalk.JAmSocNephrol.2018Mar;29(3):1049-1062.[6].ChristianPLarsen,etal.RationaldevelopmentofLEA29Y(belatacept),ahigh-affinityvariantofCTLA4-Igwithpotentimmunosuppressiveproperties.AmJTransplant.2005Mar;5(3):443-53.McePdfHeight