PDK4-IN-1-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrariesPDK4-IN-1Cat.No.:HY-135954CASNo.:2310262-10-1分?式:C??H??N?O?分?量:357.41作?靶點:PDHK;Apoptosis作?通路:MetabolicEnzyme/Protease;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性PDK4-IN-1?種蒽醌衍?物，也?種有效的，?服活性的丙酮酸脫氫酶激酶4(PDK4)抑制劑，IC50值為84nM。PDK4-IN-1有效抑制細(xì)胞轉(zhuǎn)化和細(xì)胞增殖并誘導(dǎo)細(xì)胞凋亡(apoptosis)。PDK4-IN-1具有抗糖尿病，抗癌和抗過敏作?。IC50&TargetIC50:84nM(Pyruvatedehydrogenasekinase4(PDK4))[1]體外研究PDK4-IN-1(Compound8c;50μM;0-72hours;HCT116andRKOcells)treatmentsignificantlyimpedestheproliferationofhumancoloncancercelllines,HCT116andRKO.ThecolonyformationefficiencyinHCT116andRKOcellsIssignificantlyreducedaftertreatmentofPDK4-IN-1[1].PDK4-IN-1(Compound8c;10-50μM;24hours;HCT116andRKOcells)treatmentdose-dependentlyincreasedapoptosis[1].PDK4-IN-1(Compound8c;10μM;24hours;HEK293Tcells)treatmentinhibitsphosphorylationofSer232,Ser293,andSer300ofPDHE1α[1].10μMofPDK4-IN-1(Compound8c)significantlyincreasesp-AktinAML12cells[1].PDK4-IN-1(compound8c)-inducedphosphorylationofp53onserine15isadose-dependentresponseinbothHCT116andRKOcells.PDK4-IN-1decreasestheexpressionofBCL-xLandincreasestheexpressionofBAX.CleavageofPARP1andcaspase3areincreasedbyPDK4-IN-1[1].CellViabilityAssay[1]CellLine:HCT116andRKOcellsConcentration:50μM1/3IncubationTime:0hour,24hours,48hours,72hoursResult:Significantlyimpededtheproliferationofhumancoloncancercelllines,HCT116andRKO.ApoptosisAnalysis[1]CellLine:HCT116andRKOcellsConcentration:10μM,25μM,50μMIncubationTime:24hoursResult:Dose-dependentlyincreasedapoptosis.WesternBlotAnalysis[1]CellLine:HEK293ThumanembryonickidneycellsConcentration:10μMIncubationTime:24hoursResult:InhibitedphosphorylationofSer232,Ser293,andSer300ofPDHE1α.體內(nèi)研究PDK4-IN-1(Compound8c;100mg/kg;oraladministration;daily;for1week;C57BL/6Jmice)treatmentsignificantlyimprovesglucosetolerance[1].Pre-incubationwithPDK4-IN-1(compound8c)dose-dependentlyinhibitsthereleaseofβ-hexosaminidasefromIgE/antigen-activatedBMMCs,showingthattheabsorbancevaluesare0.26,0.20,and0.126inIgE/Ag,10μM,and20μMPDK4-IN-1-treatedBMMCs[1].Thepharmacokinetic(PK)profilesofPDK4-IN-1(compound8c)areevaluatedinrat.PDK4-IN-1showsgoodbioavailability(64%),longhalf-life(>7h),andmoderateclearance(CLof0.69)inrats[1].AnimalModel:C57BL/6Jmice(8-weekold)fedwithhigh-fatdiet[1]Dosage:100mg/kgAdministration:Oraladministration;daily;for1weekResult:Significantlyimprovedglucosetolerance.REFERENCES[1].LeeD,etal.DiscoveryofNovelPyruvateDehydrogenaseKinase4InhibitorsforPotentialOralTreatmentofMetabolicDiseases.JMedChem.2019Jan24;62(2):575-588.McePdfHeight2/3Med