Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEHEMTACWEE1degrader-1Cat.No.:HY-173320CASNo.:3002417-64-0分?式:C??H??N??O?分?量:1062.27作?靶點:Wee1;HSP作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性HEMTACWEE1degrader-1?種WEE1的HSP90介導靶向嵌合體(HEMTAC)降解劑(HSP90酶抑制活性為IC50:16.76nM)。HEMTACWEE1degrader-1能促進WEE1的泛素化和降解。HEMTACWEE1degrader-1可阻斷G2/M細胞周期。HEMTACWEE1degrader-1在急性髓系??病(AML)患者來的異種移植(PDX)模型中具有抗癌活性。HEMTACWEE1degrader-1可?于AML的研究。(粉?：HSP90結合劑；藍?：WEE1配體；??：連接?)。IC50&TargetHSP9016.76nM(IC50)體外研究HEMTACWEE1degrader-1(Compound9c)(72h)inhibitstheproliferationactivityofMV-4-11cells(IC50:8.08nM)andprimaryAMLcells(IC50:4.77nM)[1].HEMTACWEE1degrader-1(0.01-10μM,12h)degradesWEE1proteininMV-4-11cellsandhasaminoreffectonAKTprotein,indicatingthatthiseffectisindependentofHSP90inhibition[1].HEMTACWEE1degrader-1(0.1-10μM,12h)promotestheexpressionofWEE1mRNAinMV-4-11cellsinaconcentration-dependentmanner[1].HEMTACWEE1degrader-1(3-30nM,72h)inducescellcyclearrestattheG2/MphaseofMV-4-11cellsinaconcentration-dependentmanner[1].WesternBlotAnalysis[1]CellLine:MV-4-11cellsConcentration:0.01μM,0.1μM,1μMand10μM1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:12hResult:Down-regulatedtheexpressionofWEE1protein.RT-PCR[1]CellLine:MV-4-11cellsConcentration:0.1μM,1μMand10μMIncubationTime:12hResult:Up-regulatedtheexpressionofWEE1mRNA.CellCycleAnalysis[1]CellLine:MV-4-11cellsConcentration:3nM,10nMand30nMIncubationTime:72hResult:InducedalargeaccumulationofcellsintheG2/Mphase.體內研究HEMTACWEE1degrader-1(Compound9c)(3mg/kg,i.v.,onceeverydayfor4weeks)hasanticanceractivitywithminimaltoxicityinamouseAMLpatient-derivedxenograft(PDX)model[1].HEMTACWEE1degrader-1(10mg/kg,i.v.,onceeverydayfor3d)hasminimalmyelosuppressivetoxicityinhealthymice[1].AnimalModel:AMLpatient-derivedxenograft(PDX)model,FemaleNOD/SCIDmice(6-9weeksold)[1]Dosage:3mg/kgAdministration:Intravenousinjection(i.v.),onceeverydayfor4weeksResult:ReducedthepercentageofhuCD45-positivecellsinthebonemarrow(>75%).Inhibitedsplenomegaly.AnimalModel:HealthymaleBALA/Cmice(20-22g)[1]Dosage:10mg/kgAdministration:Intravenousinjection(i.v.),onceeverydayfor3dResult:Hadminimaleffectonplatelets,leukocytesandneutrophilsREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].LiX,etal.Design,synthesisandbiologicalevaluationofWEE1degradersviaHSP90-mediatedtargetingchimerasfortargettherapyofacutemyeloidleukemia.EurJMedChem.2025Jun5;290:117512.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformed