BGT-002-326E-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBGT-002Cat.No.:HY-179591CASNo.:2127387-94-2Synonyms:326E分⼦式:C₁₉H₃₄O₄分⼦量:326.47作⽤靶点:ATPCitrateLyase;PPAR作⽤通路:MetabolicEnzyme/Protease;CellCycle/DNADamage;VitaminDRelated/NuclearReceptor储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性BGT-002(326E)⼀种⼝服有效的双重ACLY抑制剂和PPARα激动剂。BGT-002通过抑制合成和促进外排来减少脂⽣成。BGT-002在体内证明了其改代谢功能障碍相关性脂性肝炎和改⾼脂⾎症的功效。BGT-002可⽤于⾼胆醇⾎症和MASH的研究[1][2][3]。IC50&TargetPPARα体外研究BGT-002(3-50μmol/L,4h)inhibitsACLYactivityandsuppresseslipidsynthesisinprimaryhepatocytesisolatedfrommicebyactingasaprodrugforitsactiveACLY-inhibitingCoA-thioestermetabolite[2].BGT-002(12.5-50μmol/L,24h)increasescholesteroleffluxintheprimarymousehepatocytesbyupregulatingtheABCG5/8transporters[2].体内研究BGT-002(15,30,and60mg/kg,p.o.,dailyfor9weeks)amelioratesMASHinrodentmodelsviadualtargetingatACLYandPPARα[1].BGT-002(20mg/kg,p.o.,dailyfor18weeks)amelioratesMASHandreversesfibrosisincynomolgusmonkeys[1].BGT-002(10,30,and100mg/kg,p.o.,singledose)significantlyinhibitshepaticdenovolipogenesisinfasted-refedmice[2].BGT-002(30mg/kg,p.o.,singledoseordailyfor7days)increasescholesteroleffluxandreduceshepaticcholesterolcontentinhighcholesteroldiet-inducedmice[2].BGT-002(7.5,15,20,and30mg/kg,p.o.,dailyfor2weeks)improveshyperlipidemiaindiet-inducedhyperlipidemichamsters,andspontaneouslyhyperlipidemicrhesusmonkeys[2].1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBGT-002(15,30,and60mg/kg,p.o.,dailyfor24weeks)improvesatherosclerosisinWesterndiet(WD)-inducedApoE-/-mice[2].AnimalModel:Ob/obmicefedwithahigh-fat,highfructose,high-cholesteroldiet[1]Dosage:15,30,and60mg/kgAdministration:p.o.,dailyfor9weeksResult:Didnotsignificantlyalterbodyweightorfoodintake.SignificantlyloweredMASHdiet-inducedelevationsinALTandASTlevelsandreducedplasmalipids.NotablyreducedliverweightandNASscore.SignificantlyreducedCD68andF4/80levelsinliver,anddownregulatedtheexpressionofgenesrelatedtoliverinflammationandfibrosis.AnimalModel:Ob/obmicefedwithacholine-deficientL-aminoaciddefinedhigh-fatdiet(CDAA-HFD)[1]Dosage:15,30,and60mg/kgAdministration:p.o.,dailyfor9weeksResult:SignificantlyloweredplasmaTG,ALT,andAST,withoutchangingbodyweightorfoodintake.AlleviatedCDAA-HFDinducedhepaticsteatosisandattenuatedliverfibrosis.Significantlydownregulatedinflammatoryandfibroticgeneexpression.AlleviatedCDAA-HFD-inducedhepaticsteatosisbeyondACLY.PPARαisrequiredtoameliorateCDAA-HFD-inducedMASH.AnimalModel:MASHcynomolgusmonkeys(≥8yearsold)[1]Dosage:20mg/kgAdministration:p.o.,dailyfor18weeksResult:SteadilyloweredserumALT,AST,andγ-GTTcomparedwiththevehicle.Returnedplasmatotalcholesterol(TC)andLDL-Ctobaselineovertime.Reducedhigh-sensitivityC-reactiveprotein(hs-CRP),increasedserumBHBandFAOlevels.ResultedACLYinhibitionandPPARαactivationwithasafeprofile.AnimalModel:C57BL/6Jmicefastedfor48hfollowedbyrefeedingforanother48h[1]Dosage:10,30,and100mg/kgAdministration:p.o.,singledose2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Reducedlipogenesisspecificallyintheliverbutnotobviouslyinthemuscle,heart,ileum,abdominaladiposeorkidneytissues.AnimalModel:Malegoldenhamstersfedwithahigh-fatandhigh-cholesterol(HFHC)die[2]Dosage:7.5,15and30mg/kgAdministration:p.o.,dailyfor2weeksResult:Exhibitedadose-dependentimprovementinthehypolipidemiceffect.ReducedserumTGandHDL-Clevels.AnimalModel:Malerhesusmonkeys(6-20yearsold)withmildormoderatehyperlipidemiaformorethan2years[2]Dosage:20mg/kgAdministration:p.o.,dailyfor2weeksResult:ReducedplasmaconcentrationsofTG,LDL-CandTC.AnimalModel:ApoE-/-inducedwithWesterndiet(WD)[2]Dosage:15,30,and60mg/kgAdministration:p.o.,dailyfor24weeksResult:Significantlydecreasedbodyweightgain.SignificantlydecreasedcholesterolandLDL-Clevels.Reducedexpressionoftheinflammatory-relatedgenesCd68,F4/80andIL-1βinadosedependentmanner.REFERENCES[1].XieZ,etal.Theenedioicacidanalog326Ealleviatesmetabolicdysfunction-associatedsteatohepatitisviadualtargetingatACLYandPPARα.CellMetab.2025Nov4;37(11):2149-2166.e9.[2].XieZ,etal.DevelopmentofthenovelACLYinhibitor326Easapromisingtreatmentforhypercholesterolemia.ActaPharmSinB.2023Feb;13(2):739-753.[3].ZhuX,etal.SimultaneousdeterminationofBGT-002anditsacylglucuronidemetaboliteZM326E-M2inhumanplasmabyliquidchromatography-tandemmassspectrometryanditsapplicationtoapharmacokineticstudy.JP