AZD5582-dihydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAZD5582dihydrochlorideCat.No.:HY-110346CASNo.:1883545-51-4分?式:C??H??Cl?N?O?分?量:1088.21作?靶點(diǎn):IAP;Apoptosis作?通路:Apoptosis儲存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥50mg/mL(45.95mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM0.9189mL4.5947mL9.1894mL5mM0.1838mL0.9189mL1.8379mL10mM0.0919mL0.4595mL0.9189mL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。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(protectfromlight)。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?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，澄的儲備液可以根據(jù)儲存條件，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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(2.30mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(2.30mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(2.30mM);ClearsolutionBIOLOGICALACTIVITY?物活性AZD5582dihydrochlorideIAP拮抗劑，可以有效與cIAP1，cIAP2和XIAP的BIR3結(jié)構(gòu)域結(jié)合,IC50值分別為15，21，15nM。AZD5582誘導(dǎo)凋亡(apoptosis)[1]。IC50&TargetcIAP1cIAP2XIAP15nM(IC50)21nM(IC50)15nM(IC50)體外研究AZD5582(20nM;48hours)inhibitscellviabilitybycooperationwithIFNγorviraldouble-strandedRNA(dsRNA)inH1975NSCLCcells[2].AZD5582(20nM;17or25hours)downregulatescIAP-1,activatesRIPK1(upstreamregulatorofcaspase-8),andtriggerstheactivationofextrinsic(caspase-8)andintrinsic(caspase-9)apoptosispathways,causingthecleavageofcaspase-3andcaspase-7[2].AZD5582(20nM;48hours)involvesinapoptosisduetoinductionofcelldeathandactivecaspase-3/8activitiesbyAZD5582andIFNγco-treatmentinHCC827NSCLCcells[2].CellViabilityAssay[2]CellLine:H1975NSCLCcelllineConcentration:20nMIncubationTime:48hoursResult:CooperatedwithIFNγorviraldouble-strandedRNA(dsRNA)toinhibitcellviabilityevencelldeath.ApoptosisAnalysis[2]CellLine:HCC827NSCLCcelllineConcentration:20nMIncubationTime:48hoursResult:HadaninhibitoryeffectoncellviabilitybycooperatingwithIFNγ.WesternBlotAnalysis[2]CellLine:H1975NSCLCcelllineConcentration:20nMIncubationTime:17or25hours2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:Down-regulatedcIAP-1,activatedRIPK1(upstreamregulatorofcaspase-8),triggeredthecleavage(activation)ofcaspase-3,7,8and9.體內(nèi)研究AZD5582(intravenousinjection;0.1-3.0mg/kg;onceaweek;2weeks)causesdegradationofcIAP1andcaspase3cleavageintumorcells,andafteratwo-weektreatment,thetumorslargelyresolved;whenthemicearegivenamediumdose(0.5mg/kg)ofAZD5582,cIAP1degradesafteradministration,butittakesawhiletimetoreachapoptosis-inducingeffect[1].AnimalModel:MDA-MB-231xenograft-bearingmice[1]Dosage:0.1mg/kg,0.5mg/kg,3.0mg/kgAdministration:Intravenousinjection;onceaweek;2weeksResult:ResultedincIAP1degradationandcaspase-3cleavagewithintumorcellsandcausessubstantialtumorregressionsfollowingtwoweeklydosesof3.0mg/kg戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?MaterSciEngCMaterBiolAppl.29December2021,112615.?BiochimBiophysActaMolBasisDis.2019Jun26;1865(10):2618-2632.?CellSignal.2020Aug;72:109654.?JMolMed(Berl).2022Mar5.?ResearchSquarePreprint.2021May.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HennessyEJ,etal.DiscoveryofanovelclassofdimericSmacmimeticsaspotentIAPantagonistsresultinginaclinicalcandidateforthetreatmentofcancer(AZD5582).JMedChem.2013Dec27;56(24):9897-919.[2].QinHao,etal.IF-γandSmacmimeticssynergizetoinduceapoptosisoflungcancercellsinaTNFα-independentmanner,CancerCellInt.2018;18:84.McePdfH