SK5527-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESK5527Cat.No.:HY-179641分⼦式:C₄₂H₄₉ClF₃N₁₁O₃分⼦量:848.36作⽤靶点:PROTACs;AuroraKinase作⽤通路:PROTAC;CellCycle/DNADamage;Epigenetics储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性SK5527⼀种选择性AURKAPROTAC降解剂，可降解AURKA蛋⽩，其对AURKA的DC50=2nM。SK5527以20nM的IC50值结合NanoLuc-AURKA。SK5527能有效降低MYCN扩增型神经母细胞瘤细胞中的MYCN⽔平，但其活性受MDR1介导的外排作⽤限制。SK5527在体内能⾼效降低AURKA⽔平。SK5527可⽤于神经母细胞瘤的相关研究[1]。IC50&TargetAuroraA2nM(DC50)体外研究SK5527(0.01-10000nM,1-48h)inducesdegradationAURKAMYCNinneuroblastomaandbenigncelllinesHEK293T,RPE),exhibitsthehighpotencyinMYCN-amplifiedcells(IMR-32,NGP,SJNB-8;SK-N-BE(2)-CwithDC50s=6,2,10and73nM),showsreducedactivityinotherlines(SK-N-BE(2)-C,SK-N-AS,SJNB-1)withahookeffect,inducesMYCNdepletionasasecondarydelayedconsequenceofAURKAdegradationandrequiresconcomitantengagementofbothAURKAandCRBNtoexertthedegradationeffectinMYCNamplifiedcellsIMR-32,NGP,SJNB-8,SK-N-BE(2)-CwithGI50s=15,21,63,477nM;innon-amplifiedcellsSK-N-SH,SK-N-ASandSJNB-1withGI50s=244,654,8635nM;inbenignimmortalizedcellRPEandHEK293TwithGI50s=460and408nM[1].SK5527(10-10000nM,72h)effectivelyinhibitsneuroblastomacells(IMR-32,NGP,SJNB8,SKN-SH,SK-N-BE(2)-CandSJNB-1)growth[1].SK5527(100-1000nM,3h)requiresbothAURKAandCRBNbindingfortheactivity,significantlyengagesAURKAwithexcellentkinome-wideselectivity,upregulatesPLK1anddownregulatesHAND2andESCO2butGSPT1,CSNK1A1,ZFP91,SALL4,ZNF654,ZNF787,E4F1,andPATZ1[1].SK5527exhibitesonlymodestinhibitoryeffectsinthebenignimmortalizedcelllinesHEK293TandRPE,despitepotentAURKAdegradation,withGI50valuesofapproximately0.5μM[1].1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESK5527(10-1000nM,24-72h)islimitedbyMDR1-MediatedDrugEffluxinSKN-SH,SK-N-BE(2)-C,SJNB-1,NGP,SJNB-8,IMR-32BbutSK-N-AS(duetothelowCRBNexpression)[1].WesternBlotAnalysis[1]CellLine:IMR-32Concentration:500nMIncubationTime:1,4,24and48hResult:InducedrobustAURKAdepletionalreadyafter1h,whereasMYCNco-depletionreached50%onlyat24hpostexposure.CellProliferationAssay[1]CellLine:IMR-32,NGP,SJNB8,SKN-SH,SK-N-BE(2)-CandSJNB-1Concentration:10,100,1000and10000nMIncubationTime:72hResult:HadThestrongestantiproliferativeeffectswithGI50valuesbelow100nMconsistentwiththeobservedpotentAURKAdegradationbutlessinSKN-SH,SK-N-BE(2)-CandSJNB-1.WesternBlotAnalysis[1]CellLine:SK-N-BE(2)-C,SK-N-BE(2)-C,SK-N-SH,andSJNB-1Concentration:100nMIncubationTime:24hResult:Exhibitedhighexpressionofmultidrugresistanceprotein1(MDR1),encodedbytheABCB1geneinSK-N-BE(2)-C,SK-N-SH,andSJNB-1.ExhibitedthehighestMDR1expressioninourpanel,cotreatmentwith1μMTariquidar(HY-10550)significantlyenhancedtheAURKAdegradation.CellProliferationAssay[1]CellLine:NGPandSK-N-BE(2)-CcellsConcentration:10,100and1000nMIncubationTime:48hResult:Dose-dependentlyincreasedofcaspase3/7activity.CellProliferationAssay[1]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:NGP,SJNB-8,andSK-N-BE(2)-CConcentration:10,100and1000nMIncubationTime:72hResult:Exhibitedgrowth-inhibitoryactivitycomparabletoAURKAinhibitorTAS-119,withnearlyidenticalGI50valuesacrosscelllines.体内研究SK5527(15mg/kg,i.v.ori.p.,once)induceAURKAproteindepletioninIMR-32neuroblastomacellline-derivedxenograft(CDX)mice[1].AnimalModel:IMR-32cells(1×107cellsin0.2mLvolume)induced-femaleBALB/cnudemice[1]Dosage:15mg/kgAdministration:i.v.,ori.p.onceResult:ReducedAURKAproteinlevelsinvivoat4and8hpost-treatmentafterasingleIVdose,followedbyareturntobaselinelevelsat24hbutnotobservedini.p.groupREFERENCES[1].KrolsS,etal.Second-GenerationAURKA-TargetingPROTACs:StructuralOptimizationtowardinVivoDegradationinNeuroblastoma.JMedChem.2025Nov27;68(22):23962-23976