PROTAC-CDK2-4-6-Degrader-2-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPROTACCDK2/4/6Degrader-2Cat.No.:HY-185121CASNo.:2541626-49-5分⼦式:C₄₀H₄₅N₉O₆分⼦量:747.84作⽤靶点:PROTACs;CDK;Caspase作⽤通路:PROTAC;CellCycle/DNADamage;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PROTACCDK2/4/6Degrader-2⼀种靶向CDK2/4/6的PROTAC降解剂。PROTACCDK2/4/6Degrader-2可与特戊酸氯甲酯发⽣⼀步反应，转化为前药PROTACCDK2/4/6Degrader-1(HY-171826)。PROTACCDK2/4/6Degrader-2能够在恶性⿊⾊素瘤细胞中降解CDK2/4/6蛋⽩及其复合物，诱导细胞周期阻滞使其凋亡(apoptosis)，对⿊⾊素瘤细胞的作⽤尤为显著。PROTACCDK2/4/6Degrader-2可⽤于恶性⿊⾊素瘤的相关研究[1]。IC50&TargetCDK2CDK3CDK6Caspase3CDK4体外研究PROTACCDK2/4/6Degrader-2(compound3)(72h)exhibitsprominentanti-proliferativeactivityagainstB16F10andA375,withIC50sof0.09861and0.1659μM,respectively[1].PROTACCDK2/4/6Degrader-2(0-2000nM,0-12h)mediatesCDK2/4/6proteindegradationandimpairsdownstreamRbsignalingactivationbyhijackingtheE3ubiquitinligaseCRBNinB16F10andA375cells[1].PROTACCDK2/4/6Degrader-2(50-500nM,7days)exertssignificantanti-proliferativeactivityinB16F10andA375cells[1].PROTACCDK2/4/6Degrader-2(125-1000nM,48h)significantlyinducesapoptosisofA375andB16F10cellsinadose-dependentmannerinB16F10andA375cells[1].PROTACCDK2/4/6Degrader-2(0-2000nM,48h)inducescaspase-dependentapoptosisviathecommonP53/Bcl-2/BaxapoptoticpathwayinB16F10andA375cells[1].PROTACCDK2/4/6Degrader-2(25-1000nM,48h)inducescellcyclearrestviathedegradationofcellcycle-relatedproteinsCDK2/4/6inA375andB16F10cells[1].WesternBlotAnalysis[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:B16F10andA375cellsConcentration:0,62.5,100,125,250,500,1000and2000nMIncubationTime:0,3,6,9and12hResult:InducedsignificantintracellularcleavageofallCDK2,CDK4andCDK6proteinsinbothconcentration-dependentandtimedependentmanners.Mitigateddownstreamp-Rbsignalingpathwayactivationofmelanomacells.InducedCDK2/4/6proteindegradationviatheproteasomalpathwayat100nMand6h.CellProliferationAssay[1]CellLine:B16F10andA375Concentration:50,100,250,500nMIncubationTime:7daysResult:ExertedaremarkableinhibitingeffectoncolonyformationinA375andB16F10inlownanomolarconcentration.ApoptosisAnalysis[1]CellLine:B16F10andA375cellsConcentration:125,250,500,1000nMIncubationTime:48hResult:Significantlyinducedapoptosis.WesternBlotAnalysis[1]CellLine:B16F10andA375cellsConcentration:0,62.5,125,250,500,1000and2000nMIncubationTime:48hResult:Upregulatedcasepase-3andcleavedPARPproteinexpression.Alsosignificantlyinducedup-regulationofthepro-proteinlevelofP-53andBax.Downregulatedtheanti-apoptoticproteinlevelofBcl-2.CellCycleAnalysis[1]CellLine:B16F10andA375cellsConcentration:0,25,50,100,250,500,1000nM2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:48hResult:IncreasedaccumulationofA375cellpopulationinG0/G1phase,butG2/MphaseforB16F10cell.REFERENCES[1].WeiM,etal.Firstorallybioavailableprodrugofproteolysistargetingchimera(PROTAC)degradescyclin-dependentkinases2/4/6invivo.EurJMedChem.2021Jan1;209:112903.McePdfHeightCaution:Producthasnotbeen