Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIvarmacitinibCat.No.:HY-112724CASNo.:1445987-21-2Synonyms:SHR0302分?式:C??H??N?O?S分?量:414.48作?靶點(diǎn):JAK;Apoptosis作?通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:31.25mg/mL(75.40mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.4127mL12.0633mL24.1266mL5mM0.4825mL2.4127mL4.8253mL10mM0.2413mL1.2063mL2.4127mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(5.02mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.02mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.02mM);ClearsolutionBIOLOGICALACTIVITY?物活性Ivarmacitinib(SHR0302)?種有效的具有?服活性的JAK抑制劑，尤其JAK1的抑制劑。Ivarmacitinib對(duì)JAK1的選擇性JAK2的10倍以上，JAK3的77倍，Tyk2的420倍。Ivarmacitinib抑制JAK1-STAT3磷酸化并誘導(dǎo)肝狀細(xì)胞凋亡(apoptosis)。Ivarmacitinib具有抗增殖和抗炎作?。IC50&TargetJAK1JAK2JAK3Tyk2體外研究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?邊的抑制劑?師www.MedChemECellLine:Hepaticstellatecells(HSCs)Concentration:1nM,10nM,100nM,1μM,10μMIncubationTime:48hoursResult:Significantlyincreasedtheactivationofcaspase-3andBaxinHSCs,anddecreasedtheexpressionofBcl-2.AlsoinhibitedtheactivationofAktsignalingpathway.體內(nèi)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