SK4454-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESK4454Cat.No.:HY-179640分⼦式:C₄₂H₅₀ClF₂N₁₁O₃分⼦量:830.37作⽤靶点:PROTACs;AuroraKinase作⽤通路:PROTAC;CellCycle/DNADamage;Epigenetics储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性SK4454⼀种选择性AURKAPROTAC降解剂，可降解AURKA蛋⽩对AURKA的IC50=8nM。SK4454以20nM的IC50值结合NanoLuc-AURKA。SK4454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。SK4454在体内能⾼效降低AURKA⽔平。SK4454可⽤于神经母细胞瘤的相关研究[1]。IC50&TargetAuroraAAuroraAAuroraBCereblon20nM(IC50)1nM(Ki)7644nM(Ki)4060nM体外研究SK4454(0.01-10000nM,1-48h)inducesdegradationAURKAMYCNinneuroblastomaandbenigncelllinesHEK293T,RPE),exhibitsthehighpotencyinMYCN-amplifiedcells(IMR-32,NGP,SJNB-8;SK-N-BE(2)-CwithDC50s=6,8,23and270nM),showsreducedactivityinotherlines(SK-N-BE(2)-C,SK-N-AS,SJNB-1)withahookeffect,inducesMYCNdepletionasasecondarydelayedconsequenceofAURKAdegradationandrequiresconcomitantengagementofbothAURKAandCRBNtoexertthedegradationeffectinMYCNamplifiedcellsIMR-32,NGP,SJNB-8,SK-N-BE(2)-CwithGI50s=8,14,53,1111nM;innon-amplifiedcellsSK-N-SH,SK-N-ASandSJNB-1withGI50s=430,994,13437nM;inbenignimmortalizedcellRPEwithGI50s=221nM[1].SK4454(10-10000nM,72h)effectivelyinhibitsneuroblastomacells(IMR-32,NGP,SJNB8,SKN-SH,SK-N-BE(2)-CandSJNB-1)growth[1].SK4454(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-321/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration: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:HasThestrongestantiproliferativeeffectswithGI50valuesbelow100nMconsistentwiththeobservedpotentAURKAdegradationbutlessinSKN-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:Exhibithighexpressionofmultidrugresistanceprotein1(MDR1),encodedbytheABCB1geneinSK-N-BE(2)-C,SK-N-SH,andSJNB-1.ExhibitsthehighestMDR1expressioninourpanel,cotreatmentwith1μMTariquidar(HY-10550)significantlyenhancedtheAURKAdegradation.ApoptosisAnalysis[1]CellLine:NGPandSK-N-BE(2)-CcellsConcentration:10,100and1000nMIncubationTime:48hResult:Dose-dependentlyincreasedofcaspase3/7activity.CellProliferationAssay[1]CellLine:NGP,SJNB-8,andSK-N-BE(2)-CConcentration:10,100and1000nMIncubationTime:72h2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Exhibitedgrowth-inhibitoryactivitycomparabletoAURKAinhibitorTAS-119,withnearlyidenticalGI50valuesacrosscelllines.体内研究SK4454(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.McePdfHeightCaution: