Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEPROTACERαDegrader-4Cat.No.:HY-149295CASNo.:2521299-80-7分子式:C??H??F?N?O??S?分子量:1074.23作用靶點(diǎn):PROTACs;EstrogenReceptor/ERR;Apoptosis作用通路:PROTAC;VitaminDRelated/NuclearReceptor;Apoptosis儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性PROTACERαDegrader-4是一種高效和高選擇性的雌激素受體(EstrogenReceptor/ERR)ERα亞型PROTACs，含有OBHSAs、linker和E3連接酶配體。PROTACERαDegrader-4對(duì)Tamoxifen(HY-13757A)敏感和耐藥的ER+BC細(xì)胞和ERα突變的BC細(xì)胞具有良好的細(xì)胞抑制和ERα降解活性。PROTACERαDegrader-4能夠誘導(dǎo)自噬(Apoptosis)，可用于癌癥研究。IC50&TargetERαERβ5.08μM(Ki)26.20μM(Ki)體外研究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—您身邊的抑制劑大師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體內(nèi)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—您身邊的抑制劑大師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