Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEPROTACHER2degrader-1Cat.No.:HY-177008CASNo.:2897640-93-4分子式:C??H??N??O?分子量:910.03作用靶點:PROTACs;EGFR;Apoptosis;Akt;ERK作用通路:PROTAC;JAK/STATSignaling;ProteinTyrosineKinase/RTK;Apoptosis;PI3K/Akt/mTOR;MAPK/ERKPathway;StemCell/Wnt儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性PROTACHER2degrader-1是一種高的選擇性的HER2PROTAC類降解劑，DC50為69nM，Dmax為96%。PROTACHER2degrader-1通過持久的HER2降解和對下游通路(AKT和ERK)的強力抑制，抑制HER2陽性細胞增殖和腫瘤生長。PROTACHER2degrader-1可誘導BT-474細胞凋亡(apoptosis)。PROTACHER2degrader-1可用于HER2陽性癌癥的研究。(粉色：HER2配體：(HY-177009)；黑色：連接子；藍色：CRBN配體：(HY-W023573)[1]。IC50&TargetHER2CRBN-DDB169nM(DC50)體外研究PROTACHER2degrader-1(CompoundCH7C4)(0.1-3μM,24hours)candegradeHER2inBT-474cells,whichissuperiortoEGFRinA431cells[1].PROTACHER2degrader-1(0-10μM,72hours)hasnoinhibitoryeffectonA431cellproliferationatconcentrationsupto10μMinA431cells[1].PROTACHER2degrader-1caninhibittheproliferationofHER2-drivenbreastcancercelllinesBT-474andSK-BR-3,andgastriccancercelllineNCI-N87,withIC50valuesof0.047nM,0.098nM,and0.137nM,respectively[1].PROTACHER2degrader-1(0-100nM)inducesapoptosisofBT-474cellsandinhibitstheG1phaseoftheBT-474cellcycle[1].PROTACHER2degrader-1(0-1μM)inducesefficientHER2degradationinBT-474(DC50=69nM,Dmax=96%)andNCI-N87cells(DC50=55nM,Dmax=94%)inaconcentration-dependentmanner[1].PROTACHER2degrader-1(200nM,0-24hours)inducesHER2degradationandinhibitsAKTandERK1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEphosphorylationinBT-474cellsandNCI-N87cells[1].PROTACHER2degrader-1(200nM,24h)inducesubiquitination-mediatedHER2degradationinBT-474cellsviatheubiquitinproteasomesystem(UPS)[1].WesternBlotAnalysis[1]CellLine:A431cellsConcentration:0.1μM,0.3μM,1μM,3μMIncubationTime:24hResult:InducedalmostcompletedegradationofHER2,andasignificanthookeffectwasobservedat3μM,withoutsignificantlyaffectingEGFRlevelsinA431cells.ApoptosisAnalysis[1]CellLine:BT-474cellsConcentration:0nM,10nM,50nM,100nMIncubationTime:Result:Inducedapoptosis(63%at50nM)andinhibitedG1cellcycle(84%at100nM)inBT-474cells.WesternBlotAnalysis[1]CellLine:BT-474cells,NCI-N87cellsConcentration:10nM,100nM,250nM,1000nMIncubationTime:24hResult:InducedHER2degradationandblockedsignaltransductioninaconcentration-dependentmanner.ReducedHER2autophosphorylation.InhibitedphosphorylationofkeyHER2oncogenic-associatedkinasesAKTandERKwithoutaffectingtheirproteinlevels.WesternBlotAnalysis[1]CellLine:BT-474cells,NCI–N87cellsConcentration:200nMIncubationTime:0h,3h,6h,12h,24hResult:InducedsignificantdegradationofHER2within3h.InducedalmostcompletedegradationofHER2at24handsignificantlyinhibitedAKT2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEandERKphosphorylation.WesternBlotAnalysis[1]CellLine:BT-474cellsConcentration:200nMIncubationTime:24hResult:DegradedHER2,thisdegradationwascompletelyinhibitedafterpretreatmentwithMLN4924(HY-70062),MG132(HY-13259),lenalidomide(HY-A0003),andTucatinib(HY-16069).體內研究PROTACHER2degrader-1(CompoundCH7C4)(5mg/kg,10mg/kg,i.v.,onceaday,21days)inhibitstumorgrowthinBALB/cnudemicebearingBT-474xenografttumors[1].AnimalModel:BALB/cnudemicebearingBT-474(i.p.,1×107)xenografttumors[1]Dosage:5mg/kg,10mg/kgAdministration:i.v.,onceaday,21daysResult:Showedweakerantitumoractivitythan10mg/kgTucatinibatadoseof5mg/kg,withTGIvaluesof47%and64%,respectivelyShowedsuperiorantitumoractivitycomparedwithTucatinibatadoseof10mg/kg(TGI:73%vs.64%).DegradedHER2,andnosignificantsideeffectsorweightlosswereobservedduringtreatment.REFERENCESHuM,etal.DiscoveryofpotentandselectiveHER2PROTACdegraderbasedTucatinibwithimprovedefficacyagainstHER2positivecancers.EurJMedChem.2022Dec15;244:114775.