Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPROTACERαDegrader-12Cat.No.:HY-174453分?式:C??H??N?O?S分?量:930.34作?靶點:PROTACs;EstrogenReceptor/ERR;Apoptosis作?通路:PROTAC;VitaminDRelated/NuclearReceptor;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性PROTACERαDegrader-12?種強效且?選擇性的ERαPROTAC降解劑。PROTACERαDegrader-12對多種野?或突變型ERα的乳腺癌細胞系具有抗增殖作?，阻滯細胞周期，誘導(dǎo)細胞凋亡(apoptosis)。PROTACERαDegrader-12具有出?的抗腫瘤活性。PROTACERαDegrader-12可?于乳腺癌的研究。(粉?：ERligand-11(HY-174475)；藍?：VHLligand(HY-112078)；??：連接?(HY-W088749)；VHLligand+Linker(HY-W998310))[1]。IC50&TargetERαVHL體外研究PROTACERαDegrader-12(CompoundCP03)(0.1-10μM,24h)demonstratessignificantERαdegradationactivityinMCF-7cellswithDC50valueof1.02μM[1].PROTACERαDegrader-12(0.01-100μM,24h)exhibitspotentanticanceractivityinMCF-7cells(IC50=0.17μM)[1].PROTACERαDegrader-12exhibitsremarkablestabilityinhumanlivermicrosomesandplasmawiththelevelofplasmaproteinbindingof97.8%[1].PROTACERαDegrader-12(1-5μM,48h)haltsthecellcycleprogressionintheG1phaseandinducessubstantialcellulardeathanddamageinMCF-7[1].WesternBlotAnalysis[1]CellLine:MCF-7,MDA-MB-321,MCF-7Y537S,MCF-7D538G,MCF-7EGFR,andLCC-2celllinesConcentration:0.1,0.2,1,2,5,10μMIncubationTime:24h1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:EffectivelyinducedERαdegradationinadose-dependentmannerinMCF-7cells.EfficientlyreducedtheErαMUTlevelsinboththeMCF-7Y537SandMCF-7D538GcelllineswithDC50valuesof0.83and0.55μM,respectively.ShowedhighdegradationpotencyforERαinMCF-7EGFRandLCC-2celllines,withDC50valuesof0.13and1.40μM,respectively.WesternBlotAnalysis[1]CellLine:MCF-7Concentration:2μMIncubationTime:24hResult:WasmarkedlysuppressedinthepresenceofCoA-1orCoA-2.CellViabilityAssay[1]CellLine:MCF-7,MDA-MB-321,MCF-7Y537S,MCF-7D538G,MCF-7EGFR,andLCC-2celllinesConcentration:0.01,0.1,1,10,100μMIncubationTime:24hResult:HadnonotableinhibitoryinfluenceoncellgrowthintheER-negativecelllineMDA-MB-231atconcentrationsexceeding100μM.ExhibitedexcellentantiproliferativeactivityinMCF-7Y537S,MCF-7D538G,andMCF-7EGFR,withIC50valuesthatwere10.3-,19.4-,and58.0-foldhigherthanthoseofFul,respectively.Displayedenhancedantiproliferativeefficacyagainsttamoxifen-resistantLCC-2cells,withanIC50valuethatwas8.04-foldhigherthanthatofFulvestrant(HY-13636).RT-PCR[1]CellLine:MCF-7Concentration:0.1,1μMIncubationTime:24hResult:HadnodiscernibleimpactonthemRNAofERαexpression.ApoptosisAnalysis[1]CellLine:MCF-7,MDA-MB-321,MCF-7Y537S,MCF-7D538G,MCF-7EGFR,andLCC-2celllinesConcentration:1,5μM2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:48hResult:Inducedsubstantialcellulardeathanddamageinaconcentration-dependentmanner.EffectivelyhaltedthecellcycleprogressionintheG1phase.體內(nèi)研究PROTACERαDegrader-12(CompoundCP03)(1-4mg/kg,i.p.,everyotherdayfor26or33days)exhibitssignificanttumor-inhibitoryeffectsinmiceMCF-7andLCC-2tumorxenograftmodels[1].AnimalModel:MCF-7andLCC-2tumorxenograftmodels,FemaleBALB/cnudemice(15-18g,5weeksold)[1]Dosage:1,2,4mg/kgAdministration:Intraperitonealinjection(i.p.),everyotherday,for26or33days.Result:Showedsignificanttumorgrowthinhibitoryactivityat2mg/kg.Hadnosignificanthosttoxicityasmonitoredbychangesinthebodyweight.Almostcompletelyinhibitedtumorgrowthonday33atadoseof2or4mg/kg.EffectivelyinducedsignificantdegradationofERαwith2mg/kg.REFERENCES[1].WangY,etal.TargetedDegradationoftheEstrogenReceptorαthroughUnconventionalCoactivatorBindingSite(CBS).JMedChem.2025Jul10;68(13):13640-13660.McePdfHeigh