PIN1-degrader-3-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPIN1degrader-3Cat.No.:HY-179577CASNo.:3101950-55-1分⼦式:C₃₁H₃₄Cl₂N₆O₄分⼦量:625.55作⽤靶点:PIN1作⽤通路:PI3K/Akt/mTOR储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PIN1degrader-3⼀种Pin1(肽脯氨酰异构酶蛋⽩)降解剂(IC50=4.65nM)。PIN1degrader-3与Pin1共价结合。PIN1degrader-3可在体外使Pin1不稳定，从⽽导致其在细胞内降解。PIN1degrader-3可⽤于胰腺癌的研究[1]。IC50&TargetPin14.65nM(IC50)体外研究PIN1degrader-3(Compound164B8;CompoundH-3-V)(250μM,3h)bindstoPin1,causingaconformationalchangethataffectstheloopFGandhelixDregions[1].PIN1degrader-3(0-15μM,24h)effectivelyinducesdose-dependentdegradationofMIAPaCa-2andPin1inhumanpancreaticcancercelllineBxPC3andmousepancreaticcancercelllineKPC[1].PIN1degrader-3(5μM,24h)-inducedPin1degradationinBxPC3andKPCcelllinesisreversible[1].PIN1degrader-3(0.5-10μM,24h)inducesdose-dependentdegradationofPin1inallCAFs(Cancer-AssociatedFibroblasts)(CAF-BTGforcholangiocarcinoma,CAF-APPforappendicealcancer,andCAF-COLforcolorectalcancer)[1].PIN1degrader-3(72h)-inducedPin1degradationreducedcellviability,withEC50valuesof8.4μMinMIAPaCa-2cellsand5.3μMinKPCcelllines[1].WesternBlotAnalysis[1]CellLine:BxPC3cells,MIAPaCa-2cells,KPCcellsConcentration:0μM,0.5μM,1μM,3μM,5μM,10μM,15μM1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:24hResult:Pin1proteinlevelsdecreasedinadose-dependentmannerinallthreecelllines.体内研究PIN1degrader-3(Compound164B8;CompoundH-3-V)(30-60mg/kg,i.p.,onceaday,5daysaweek,for2weeks)caneffectivelyinhibitKPCcellallografttumors,reducetumorburden,anddirectlyleadtothedegradationofPin1intumortissue,buthighdosesmaycausehematologicaltoxicity[1].AnimalModel:MaleNSGmicewereusedtoestablishaperitonealmetastasismodelbyintraperitonealinjectionofKPCpancreaticcancercellsexpressingGFPandluciferase[1].Dosage:30mg/kg,60mg/kgAdministration:I.p.,onceaday,5daysaweek,for2weeksResult:Tumorburdendecreasedsignificantlyinadose-dependentmanner.Mildanemiaandmoderatethrombocytopeniaoccurredinthe60mg/kggroup.REFERENCES[1].AlboreggiaG,etal.Pre-clinicalevaluationofapotentandeffectivePin1-degradingagentinpancreaticcancer.MolTherOncol.2025Nov1;33(4):201078.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.For