JAK3-covalent-inhibitor-2-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEJAK3covalentinhibitor-2Cat.No.:HY-161354CASNo.:2664050-97-7分子式:C₂₀H₂₀N₆O₃分子量:392.41作用靶点:JAK;Apoptosis作用通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt;Apoptosis储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性JAK3covalentinhibitor-2(compoundJ1b)是一种选择性、口服有效的JAK3抑制剂(IC50=7.2nM)，具有低毒性、抗炎活性和良好的生物利用度[1]。IC50&TargetJAK37.2nM(IC50)体外研究JAK3covalentinhibitor-2showslowcytotoxicityamongHEK293,LO2,chondrocytesandRAW264.7withIC50s(72h)of86.82μM(HEK293),61.79μM(LO2),>32μM(chondrocytes)and>32μM(RAW264.7)respectively[1].JAK3covalentinhibitor-2(100mM;90min)showst1/2of13.1minand43.9mininhumanandratlivermicrosomes,respectively.Andthecleanrateof132.5mL/min/kgandmL/min/kg,resepectively[1].JAK3covalentinhibitor-2((0.125-8μM;48h))dose-dependentlyinducesTlymphocytesapoptosis[1].ApoptosisAnalysis[1]CellLine:CD4+Tcells,CD8[1]TcellsConcentration:0.125,0.5,1,2,4,8μMIncubationTime:48hResult:Dose-dependentlyledtoapoptosisamongCD4+andCD8+Tcells体内研究Anti-inflammatoryactivity:JAK3covalentinhibitor-2(30mg/kg,p.o.;singledose)inhibitedcarrageenan-1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEinducedpawedemainICRmice,witharapidreductioninpawthicknessinJ1b-treatedmice[1].Toxicity:JAK3covalentinhibitor-2(2g/kg,p.o.;singledose)Liverandkidneyappearetobesimilartothoseofnormalmice,noweightlossorotheradverseeffectsareobserved[1].Pharmacokinetics:JAK3covalentinhibitor-2(5mg/kg;p.o.),clearance(Cl)7.37l/h/kg,oralhalf-life(t1/2=3.77h),andbioavailability(F=31.69%)[1].PharmacokineticparametersofcompoundJAK3covalentinhibitor-2inSDrats[1]JAK3covalentinhibitor-2在SD大鼠体内的药代动力学分析[1]RouteDose(mg/kg)Cmax(mg/L)tmax(h)t1/2(h)AUC0-t(mg/L·h)VCl,Cl/F(L/h/kg)F(%)i.v.54497.320.082.632161.388.98(V)2.32V(Cl)31.69p.o.5501.80.253.77684.8739.89(V/F)7.37(Cl/F)/Treatmentofarthritis:JAK3covalentinhibitor-2(60mg/kg,p.o.onceaday)inCIAmodelalmostcompleterestorationofnormaljointstatusisachieved,andnosignificantweightchangesorotheradverseeffectsareobserved[1].AnimalModel:ICRmice[1]Dosage:30mg/kgAdministration:p.o.Result:Showedsignificantanti-inflammatoryactivitybyoraladministration.AnimalModel:C57BL/6mice[1]Dosage:2g/kgAdministration:p.o.Result:Inhibitedtumorgrowth.Liversandkidneysappearedtobesimilartothoseofnormalmice.Noweightlossorotheradverseeffectswereobserved.AnimalModel:SDrats[1]Dosage:5mg/kgAdministration:p.oResult:JAK3covalentinhibitor-2hadgoodintestinalabsorptionandoralbioavailability.Clearancerate(Cl)was7.37L/h/kg,oralhalf‐life(t1/2=3.77h),F=31.69%AnimalModel:CIAmodelmouse[1]Dosage:JAK3covalentinhibitor-2(30mg/kg),JAK3covalentinhibitor-2(60mg/kg,)Tofacitinib（HY-40354）(30mg/kg)2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEAdministration: p.o.Result: JAK3covalentinhibitor-2groupat60mg/kghistopathologicalanalysisshowedthatthejointhadreturnedtoalmostnormalconditions.REFERENCESHualiangYetal.DesignandsynthesisofhighlyselectiveJanuskinase3covalentinhibitorsforthetreatmentofrheumatoidarthritisARCHPHARM.2024Febe2300753McePdfHeightCaution:Producthasno