Ivarmacitinib-SHR0302-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEIvarmacitinibCat.No.:HY-112724CASNo.:1445987-21-2Synonyms:SHR0302分⼦式:C₁₈H₂₂N₈O₂S分⼦量:414.48作⽤靶点:JAK;Apoptosis作⽤通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:31.25mg/mL(75.40mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4127mL12.0633mL24.1266mL5mM0.4825mL2.4127mL4.8253mL10mM0.2413mL1.2063mL2.4127mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(5.02mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.02mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.02mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Ivarmacitinib(SHR0302)⼀种有效的具有⼝服活性的JAK抑制剂，尤其JAK1的抑制剂。Ivarmacitinib对JAK1的选择性JAK2的10倍以上，JAK3的77倍，Tyk2的420倍。Ivarmacitinib抑制JAK1-STAT3磷酸化并诱导肝状细胞凋亡(apoptosis)。Ivarmacitinib具有抗增殖和抗炎作⽤。IC50&TargetJAK1JAK2JAK3Tyk2体外研究Ivarmacitinib(SHR0302;1nM-10µM;48hours;HSCs)treatmentdisplaysaninhibitoryeffectontheproliferationofHSCsinaconcentration-dependentmanner[2].Ivarmacitinib(1nM-10µM)exertsaninhibitoryeffectontheactivation,proliferationandmigrationofHSCs[2].Ivarmacitinib(1nM-10µM;48hours;HSCs)treatmentinducestheapoptosisofHSCs[2].Ivarmacitinib(1nM-10µM;48hours;HSCs)treatmentsignificantlyincreasestheactivationofcaspase-3andBaxinHSCs,anddecreasestheexpressionofBcl-2.SHR0302alsoinhibitstheactivationofAktsignalingpathway[2].CellProliferationAssay[2]CellLine:Hepaticstellatecells(HSCs)Concentration:1nM,10nM,100nM,1µM,10µMIncubationTime:48hoursResult:DisplayedaninhibitoryeffectontheproliferationofHSCs,andthatinhibitionocurredinaconcentration-dependentmanner.ApoptosisAnalysis[2]CellLine:Hepaticstellatecells(HSCs)Concentration:1nM,10nM,100nM,1µM,10µMIncubationTime:48hoursResult:InducedtheapoptosisofHSCs.WesternBlotAnalysis[2]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:Hepaticstellatecells(HSCs)Concentration:1nM,10nM,100nM,1µM,10µMIncubationTime:48hoursResult:Significantlyincreasedtheactivationofcaspase-3andBaxinHSCs,anddecreasedtheexpressionofBcl-2.AlsoinhibitedtheactivationofAktsignalingpathway.体内研究Ivarmacitinib(SHR0302;0.3-3.0mg/kg;intragastricadministration;twiceaday;for14days;maleSprague-Dawley(SD)rats)treatmentsuppressestheseverityofAAratsbyattenuatingthearthritisindex,arthritisglobalassessmentandpawswellingdegree,andalleviatedhistopathologyofspleenandjointofAArats[1].IvarmacitinibcaninhibittheproliferationofT,Bandfibroblast-likesynoviocytes(FLS),anddown-regulatescytokinesTNF-α,IL-1β,IL-17andantibodyIgG1,IgG2alevels,andsuppressestheproportionofTh17andtotalB,andinhibitsJAK1-STAT3phosphorylation[1].AnimalModel:MaleSprague-Dawley(SD)rats(150-180g)injectedwithcompleteFreund’sadjuvant(CFA)[1]Dosage:0.3mg/kg,1.0mg/kg,3.0mg/kgAdministration:Intragastricadministration;twiceaday;for14daysResult:Suppressedtheseverityofadjuvant-inducedarthritis(AA)ratsbyattenuatingthearthritisindex,arthritisglobalassessmentandpawswellingdegree,andalleviatedhistopathologyofspleenandjointofAArats.REFERENCES[1].HuaxunWu,etal.JAK1-STAT3BlockadebyJAKInhibitorSHR0302AttenuatesInflammatoryResponsesofAdjuvant-InducedArthritisRatsandDecreasesTh17andTotalBCells.JointBoneSpine.2016Oct;83(5):525-32.[2].Yuan-JingGu,etal.TargetedBlockadeofJAK/STAT3SignalingInhibitsProliferation,MigrationandCollagenProductionasWellasInducingtheApoptosisofHepaticStellateCells.IntJMolMed.2016Sep;38(3