PROTAC-ERα-Degrader-4-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEPROTACERαDegrader-4Cat.No.:HY-149295CASNo.:2521299-80-7分子式:C₅₅H₆₂F₃N₅O₁₀S₂分子量:1074.23作用靶点:PROTACs;EstrogenReceptor/ERR;Apoptosis作用通路:PROTAC;VitaminDRelated/NuclearReceptor;Apoptosis储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性PROTACERαDegrader-4是一种高效和高选择性的雌激素受体(EstrogenReceptor/ERR)ERα亚型PROTACs，含有OBHSAs、linker和E3连接酶配体。PROTACERαDegrader-4对Tamoxifen(HY-13757A)敏感和耐药的ER+BC细胞和ERα突变的BC细胞具有良好的细胞抑制和ERα降解活性。PROTACERαDegrader-4能够诱导自噬(Apoptosis)，可用于癌症研究。IC50&TargetERαERβ5.08μM(Ki)26.20μM(Ki)体外研究PROTACERαDegrader-4(1μM,12hours)exhibitssignificantdegradationactivityforERαinMCF-7cells[1].PROTACERαDegrader-4(2μM,12hours)candegradewild-typeERαinT47DcellsandmutantERαinT47DD538GandT47DY537Scells[1].PROTACERαDegrader-4(0.01-10μM,72hours)hasinhibitoryactivityofERαinTamoxifen-sensitiveMCF-7cells,withtheIC50valueof0.05μM[1].PROTACERαDegrader-4(1-10μM,72hours)induceapoptosisandcellcyclearrestofMCF-7cells[1].PROTACERαDegrader-4(0.01-10μM,12hours)efficientlydegradesERαproteinintherangeof0.01to10μMinMCF-7cellline[1].PROTACERαDegrader-4(unknown,6hours)decreasesthenascentRNAsynthesisofERαtargetgenes,anddisplaysstronginhibitoryeffectsonPolIIandH3K27aclevels[1].CellViabilityAssay[1]CellLine:MCF-7cells1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEConcentration:0.01-10μMIncubationTime:72hoursResult:HadinhibitoryactivityinTamoxifen-sensitiveMCF-7cells,withtheIC50valueof0.05μM.ApoptosisAnalysis[1]CellLine:MCF-7cellsConcentration:1.0μM,5μM,5.0μMIncubationTime:72hoursResult:Inducedapoptosis.CellCycleAnalysis[1]CellLine:MCF-7cellsConcentration:0.01-10μMIncubationTime:72hoursResult:Inducedcellcyclearrest.WesternBlotAnalysis[1]CellLine:MCF-7cellsConcentration:0.01-10μMIncubationTime:12hoursResult:EfficientlydegradedERαproteinintherangeof0.01to10μM,whereasERαproteinlevelsrecoveredslightlyatahighconcentrationof10μM体内研究PROTACERαDegrader-4(CompoundZD12)(5μM/kgfori.p.,onceevery2days)exhibitspotentantitumoractivityandERαdegradationeffectintumortissuesinLCC2orthotopicxenografttumormodels[1].PROTACERαDegrader-4(5mg/kgfori.v.)showsaT1/2of4.61handCLof64.4mL/min/kg[1].AnimalModel:LCC2orthotopicxenografttumormodels[1]Dosage:5μM/kgAdministration:Intravenousinjection(i.p.)2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEResult:ExhibitedpotentantitumoractivityandERαdegradationeffectintumortissues.AnimalModel:BALB/Cfemalemice(Pharmacokineticassay)[1]Dosage:5mg/kg;20mg/kgAdministration:Intravenousinjection(i.v.);Oralgavage(p.o.)Result:PharmacokineticparametersforPROTACERαDegrader-4(CompoundZD12)inBALB/Cfemalemice[1]RouteDose(mg/kg)CL(mL/min/kg)Tmax(h)T1/2(h)Cmax(ng/mL)AUC(h•ng/mL)i.v.564.40.084.613635.731342p.o.20NDNDNDNDNDND:notdetected.REFERENCESXieB,et.al.DiscoveryofaNovelClassofPROTACsasPotentandSelectiveEstrogenReceptorαDegraderstoOvercomeEndocrine-ResistantBreastCancerInVitroandInVivo.JMedChem.2023May25;66(10):6631-6651.McePdfHeightCaution:Producthasnotbeen