JAK3-IN-11-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEJAK3-IN-11Cat.No.:HY-146727CASNo.:2412734-00-8分⼦式:C₂₃H₂₃N₅O₂分⼦量:401.46作⽤靶点:JAK作⽤通路:Epigenetics;JAK/STATSignaling;StemCell/Wnt储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性JAK3-in-11(Compound12)⼀种有效的、⽆细胞毒性、不可逆、具有⼝服活性的JAK3抑制剂，IC50值为1.7nM，具有优良的选择性(⾼于其他JAK3亚型的588倍)，共价结合到JAK3的ATP-bindingpocket。JAK3-IN-11强烈抑制JAK3依赖的信号转导和T细胞增殖，研究⾃⾝免疫性疾病的有效⼯具[1]。IC50&TargetJAK3JAK2JAK11.7nM(IC50)1μM(IC50)1.32μM(IC50)体外研究JAK3-IN-11(Compound12)(10μM,72h)hasnoobviouscytotoxicityataconcentrationof10μM[1].JAK3-IN-11(Compound12)(72h)displaysstronginhibitionforTcellproliferationwithIC50valuesof0.83μM(anti-CD3/CD28stimulation)and0.77μM(IL-2stimulation)[1].JAK3-IN-11(Compound12)(0-10μM,1h)abrogatesIL-2orIL-15-inducedphosphorylationofSTAT5inaconcentration-dependentmanner[1].JAK3-IN-11(Compound12)covalentlybindstoJAK3andirreversiblyinhibitsJAK3[1].CellProliferationAssay[1]CellLine:MouseTcellsincompleteRPMI1640mediumthenexposedtoanti-CD3/anti-CD28orIL-2.Concentration:IncubationTime:72h.Result:DisplayedstronginhibitionforTcellproliferationwithanIC50valuesof0.83μM(anti-1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECD3/CD28stimulation)and0.77μM(IL-2stimulation),showedobvioussignificantimmunosuppressiveactivityunderselectiveinhibitionofJAK3.WesternBlotAnalysis[1]CellLine:PurifiedTcellswerepre-activatedcoatedwithanti-CD3andanti-CD28for72h,thenculturedwithIL-2(50U/mL)for36h,then,culturedwithoutIL-2for36hConcentration:0.01,0.1,1,10μM.IncubationTime:1h.Result:AbrogatedIL-2orIL-15-inducedphosphorylationofSTAT5inaconcentration-dependentmanner.体内研究JAK3-IN-11(Compound12)(Oxazolone(OXZ)-inducedDTHBalb/cmice;0-30mg/kg;PO,priortoandduringthechallengephase,6days)inhibitsoxazolone(OXZ)-induceddelayedtypehypersensitivity(DTH)responsesinadose-dependentmanner[1].AnimalModel:Oxazolone(OXZ)-inducedDTHBalb/cmicemodel[1].Dosage:30,10,and3mg/kg.Administration:PO,priortoandduringthechallengephase,6days.Result:Inhibitedoxazolone(OXZ)-induceddelayedtypehypersensitivity(DTH)responsesinadose-dependentmanner.AnimalModel:MaleICRmice[1].Dosage:30mg/kgfororalgavage,10mg/kgforintravenousadministration.Administration:PharmacokineticAnalysisResult:PreliminarypharmacokineticdataofJAK3-IN-11(Compound12)inmaleICRMice[1]MaleICRmice,30mg/kgfororalgavage,10mg/kgforintravenousadministration[1].Compound12iv(10mg/kg)po(30mg/kg)AUC(0-t)(mg/L*h)a1244.41±77.83889.42±48.32AUC(0-∞)(mg/L*h)1274.41±57.18897.12±56.72MRT(0-∞)(h)b0.73±0.081.42±0.38Vz(L/kg)c8.36±1.83220.42±24.71CLz(L/h/kg)d8.15±1.2197.14±20.87t1/2(h)e0.47±0.061.52±0.34Cmax(mg/L)f8763.23±324.652008.21±189.44Bioavailability(%)g23.82%aAreaundertheconcentrationtimecurve.bMeanresidencetime.cVolumeinsteadystate.dPlasmaclearance.eTerminalhalf-life.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEfPeakplasmaconcentrations.gBioavailability=AUC0-t(po)/AUC0-t×100%.REFERENCES[1].LeiShu,etal.Design,synthesis,andpharmacologicalevaluationof4-or6-phenyl-pyrimidinederivativesasnovelandselectiveJanuskinase3inhibitors.EurJMedChem.2020Apr1;191:112148.McePdfHeightCaution:Producthas