PROTAC-HMGCR-Degrader-2-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPROTACHMGCRDegrader-2Cat.No.:HY-181134CASNo.:2715104-46-2分⼦式:C₅₃H₇₉N₅O₁₀S分⼦量:978.29作⽤靶点:PROTACs作⽤通路:PROTAC储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PROTACHMGCRDegrader-2⼀种靶向HMGCR的PROTAC降解剂，其IC50为0.25μM。PROTACHMGCRDegrader-2可在Insig因沉默的⼈肝癌细胞(HepG2)中降解HMGCR，DC50为0.12μM。PROTACHMGCRDegrader-2的⼝服前药PROTACHMGCRDegrader-1(HY-171823)。PROTACHMGCRDegrader-2可通过缺氧诱导因⼦脯氨酰羟化酶(VHL)依赖的泛素-蛋⽩酶体系统降解HMGCR，并降低⼈肝癌细胞(HepG2)内的胆醇⽔平。PROTACHMGCRDegrader-2可⽤于⾼⾎脂症相关研究[1]。IC50&TargetVHL体外研究PROTACHMGCRDegrader-2(compound21c)(0.01-3μM,16h)preferentiallyactsasHMGCRinhibitorsoverdegradersathighdosesinHepG2cells,achievesamaximumdegradation(Dmax)of65%atahighdoseof1μM[1].PROTACHMGCRDegrader-2(0.1μM,24h)reducescellularcholesterolinHepG2cells[1].PROTACHMGCRDegrader-2(0.01-3μM,0-48h)inducesPROTAC-mediatedHMGCRdegradationinInsig-silencedHepG2cellswithaDC50of0.12μM,andachievedaDmaxof76%at1μM[1].PROTACHMGCRDegrader-2(1μM,6h)bindssimultaneouslytoHMGCRandVHL,andsubsequentlydegradedHMGCRbytheVHL-dependentubiquitin-proteasomesysteminInsig-silencedHepG2cells[1].WesternBlotAnalysis[1]CellLine:HepG2cellsConcentration:0.01,0.03,0.1,0.3,1and3μMIncubationTime:16h1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:AttenuatedtheupregulationofHMGCRatlowdosesandincreasedHMGCRexpressionathighdoses.WesternBlotAnalysis[1]CellLine:HepG2cellsConcentration:0.01μMIncubationTime:24hResult:Reducedcellularcholesterolproteinexpression.WesternBlotAnalysis[1]CellLine:Insig-silencedHepG2cellsConcentration:0.01,0.03,0.1,0.3,1and3μMIncubationTime:0,4,8,16,24and48hResult:EffectivelydegradedtheHMGCRproteinatadosemannerconcentrationand16h.ElevatedHMGCRexpressionathigherconcentrationof3μM.ReducedHMGCRproteinlevelinatime-dependentmannerat1μM.WesternBlotAnalysis[1]CellLine:HepG2cellsConcentration:1μMIncubationTime:16hResult:EffectivelyattenuatedthecompensatoryupregulationofHMGCR.WesternBlotAnalysis[1]CellLine:Insig-silencedHepG2cellsConcentration:1μMIncubationTime:16hResult:InducedHMGCRdegradation,whichwassignificantlyblockedbytheadditionofVHL032(10μM)orMG132(10μM)(HY-13259).InducedHMGCRdegradationreducedbylovastatin(HY-N0504).REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].LuoG,etal.DiscoveryofanorallyactiveVHL-recruitingPROTACthatachievesrobustHMGCRdegradationandpotenthypolipidemicactivityinvivo.ActaPharmSinB.2021May;11(5):1300-1314.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical