PDK1-IN-5-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPDK1-IN-5Cat.No.:HY-179501分⼦式:C₁₆H₁₂Cl₂F₃NO₃分⼦量:394.17作⽤靶点:PDK-1;ReactiveOxygenSpecies(ROS);Apoptosis;OxidativePhosphorylation作⽤通路:PI3K/Akt/mTOR;Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PDK1-IN-5⼀种选择性PDK1抑制剂。PDK1-IN-5通过抑制PDK1降低磷酸化⽔平从⽽激活PDH。PDK1-IN-5能有效逆转Warburg效应，通过增加⼄酰辅酶A、减少乳酸、升⾼线粒体ROS并随后诱导细胞凋亡(apoptosis)，将细胞能量代谢从糖酵解(oxidativephosphorylation)转向氧化磷酸化。PDK1-IN-5在体内能强效抑制肿瘤⽣长且不引起系统性毒性。PDK1-IN-5可⽤于肺腺癌、⼈⾮⼩细胞肺腺癌以及胃癌和结直肠癌的研究[1]。体外研究PDK1-IN-5(compoundD16)(48h)showsselectivityandsuperiorantiproliferativeactivityinA549(lungadenocarcinoma),PC9(lungadenocarcinoma),H1975(humannon-smallcelllungadenocarcinoma),HGC-27(gastric),andHCT-116(colorectal)withIC50sof0.86,5.99,4.92,2.48and1.15μM,respectively[1].PDK1-IN-5(1μM)exhibitsstrongPDK1inhibitoryactivitywithinhibiton=53.20%[1].PDK1-IN-5(0-12μM,0.5h)activatesPDHbydiminishingthephosphorylationlevelofPDHviainhibitionofPDK1activityinA549andPC9cells[1].PDK1-IN-5(0.4-1.6μM,14days)suppressesaconcentration-dependentproliferativecapacityinA549andPC9cells[1].PDK1-IN-5(0.4-1.6μMand3-12μM,24h)inhibitscellularmigrationofbothA549andPC9cellsinadose-dependentfashion[1].PDK1-IN-5(0.2-3.2μMand1.5-24μM,48h)elevatesmitochondrialROSlevelsandinducesconcentration-dependentapoptosis[1].PDK1-IN-5(0.2-3.2μMand1.5-24μM,24and48h)effectivelychangestumorcellmetabolismbyreversingtheWarburgeffectthroughpotentPDK1inhibition,shiftingtheenergybalancefromglycolysistowardOXPHOSandhighlightingitstherapeuticpotential[1].WesternBlotAnalysis[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:A549andPC9cellsConcentration:0,0.4,0.8and1.6μM(A549);0,3,6,12μM(PC9)IncubationTime:0.5hResult:DecreasedtheexpressionofphosphorylatedproteinpPDH(serine293)inaconcentration-dependentmanner.ReducedphosphorylationlevelandraisedPDHA1expression.CellProliferationAssay[1]CellLine:A549andPC9cellsConcentration:0,0.4,0.8and1.6μM(A549);0,3,6,12μM(PC9)IncubationTime:14daysResult:Achieved98%inhibitionofcolonyformationat14dayinhighconcentrationtreatment(1.6μM).CellMigrationAssay[1]CellLine:A549andPC9cellsConcentration:0,0.4,0.8and1.6μM(A549);0,3,6,12μM(PC9)IncubationTime:24hResult:Reached80.5%inhibitionatthehighestconcentration.CellCytotoxicityAssay[1]CellLine:A549andPC9cellsConcentration:0.2,0.8and3.2μM(A549);1.5,6,24μM(PC9)IncubationTime:48hResult:InducedPC9cellsapoptoticrateat1.5,6,and24μMwith7.0%,12.5%,and17.7%,respectively.InducedA549cellsapoptoticrateat0.2,0.8,and3.2μMwith16.1%,26.6%,and30.7%,respectively.体内研究PDK1-IN-5(compoundD16)(5-20mg/kg,i.p.,every2daysfor14days)exertsanti-tumoreffectsinvivothroughinhibitionoftumorproliferationinA549andPC9xenograftmousemodels[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:MaleBALB/c-nunudemice(4weeksold)wereimplantedwithA549andPC9cells[1].Dosage:5,10,and20mg/kgAdministration:i.p.,every2daysfor14daysResult:RevealednopathologicalabnormalitiesinHematoxylin-Eosin(H&E)inmajororgans(heart,liver,spleen,lung,kidney)fromthe20mg/kg.Maintainedstablebodyweightsinanimalsthroughouttheexperimentalperiod.DownregulatedPDK1expressionandreducedthenumberofKi-67-positivecellsintreatedtumors.REFERENCES[1].TangM,etal.ReversingtheWarburgeffect:Discoveryofpotentpyruvatedehydrogenasekinaseinhibitorsforinhibitingtumorgrowth.BioorgChem.2025Dec;167:109224.McePdfHeightCa