Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemESC99Cat.No.:HY-124858CASNo.:882290-02-0分?式:C??H?Cl?FN?O分?量:336.15作?靶點(diǎn):STAT;JAK;Apoptosis作?通路:JAK/STATSignaling;StemCell/Wnt;Epigenetics;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:83.33mg/mL(247.90mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.9749mL14.8743mL29.7486mL5mM0.5950mL2.9749mL5.9497mL10mM0.2975mL1.4874mL2.9749mL請(qǐng)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，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)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，配制前請(qǐng)先配制澄的儲(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，體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分?指該溶劑在您配制終溶液中的體積占?)：1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.08mg/mL(6.19mM);Suspendedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(6.19mM);Suspendedsolution;Needultrasonic1/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性SC99?服有效的，選擇性的STAT3抑制劑，靶向JAK2-STAT3途徑。SC99結(jié)合在JAK2的ATP結(jié)合袋中。SC99抑制JAK2和STAT3的磷酸化，?對(duì)與STAT3信號(hào)相關(guān)的其他激酶沒(méi)有響。SC99抑制??板活化、聚集，并顯?有效的抗?髓瘤，抗?栓形成活性。IC50&TargetSTAT3JAK2體外研究SC99(10or30μM;for72hours)inducesMMcelldeath[1].SC99(10μM;24hours)decreasesthep-STAT3levelbuthasnoeffectsontotalSTAT3expression.SC99(2.5,5,10,20μM;for60mins)inhibitsJAK2phosphorylationinaconcentration-dependentmannerbutdoesnotinhibitthephosphorylationlevelsofAKT,ERK,mTORorc-Srcataconcentrationupto20μM[1].SC99(1.25,2.5,5μM;pre-treatedfor10min)inhibitscollagen(2μg/mL)andthrombin(0.02U/mL)inducedphosphorylationofSTAT3inaconcentration-dependentmanner[2].SC99(pre-treatedfor2hours)inhibitsIL-6(50ng/ml;for20min)inducedSTAT3nucleartranslocationinOPM2cells[3].ApoptosisAnalysis[1]CellLine:Sixmultiplemyeloma(MM)celllines(LP1,JJN3,RPMI-8226,U266,OPM2andOCI-MY5)Concentration:10or30μMIncubationTime:For72hoursResult:InducedMMcelldeath.ApoptosisAnalysis[1]CellLine:MMcelllines[1]Concentration:10μMIncubationTime:24hoursResult:Decreasedthep-STAT3levelbuthadnoeffectsontotalSTAT3expressioninallcelllinesexamined.體內(nèi)研究SC99(30mg/kg;orally;daily;forcontinuous14or28days)delaysmyelomatumorgrowthinxenograftmicemodels[1].SC99(5,10,?15mM,15?μL;ICV)producesaneffectiveinhibitoryeffectonthephosphorylationofJAK2andSTAT3inmiddlecerebralarteryocclusionandreperfusion(MCAO/R)model(adultmaleSDrats;250-300?g).SC99amelioratesneuronalapoptosisanddegeneration,neurobehavioraldeficits,inflammatoryresponseandbrainedema[3].AnimalModel:NudemicewithHumanMMcellsOPM2orJJN3[1]2/3MasterofSmallMolecules—您?邊的抑制劑?師www.MedChemEDosage:30mg/kgAdministration:Orally;daily;forcontinuous14or28daysResult:Delayedmyelomatumorgrowthinxenograftmicemodelsandsuppressedtumorgrowthmorethan40%in14daysintheOPM2model.REFERENCES[1].ZubinZhang,etal.Anovelsmallmoleculeagentdisplayspotentanti-myelomaactivitybyinhibitingtheJAK2-STAT3signalingpathway.Oncotarget.2016Feb23;7(8):9296-308.[2].ZhuanXu,etat.AnovelSTAT3inhibitornegativelymodulatesplateletactivationandaggregation.ActaPharmacolSin.2017May;38(5):651-659.[3].YipingDing,etal.EffectsofSC99oncerebralischemia-perfusioninjuryinrats:SelectivemodulationofmicrogliapolarizationtoM2phenotypeviainhibitingJAK2-STAT3pathway.NeurosciRes.2019May;142:58-68.McePdfHeightCaution:Prod