Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEABP/PPARmodulator1Cat.No.:HY-172883分?式:C??H??NO?分?量:561.67作?靶點:FABP;PPAR作?通路:MetabolicEnzyme/Protease;CellCycle/DNADamage;VitaminDRelated/NuclearReceptor儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性ABP/PPARmodulator1?種具有?服活性的FABP和PPAR多重調(diào)節(jié)劑(FABP1和FABP4的IC50分別為0.65μM和1.08μM，PPARα、PPARγ和PPARδ的EC50分別為9.19μM、2.20μM和1.58μM)。ABP/PPARmodulator1具有強效的抗代謝功能障礙相關(guān)脂性肝炎(MASH)活性。ABP/PPARmodulator1劑量依賴性地改WD+Carbontetrachloride誘導的MASH??模型脂肝的多種病理特征[1]。IC50&TargetPPARαPPARγPPARδFABP19.19μM(EC50)2.20μM(EC50)1.58μM(EC50)0.65μM(IC50)FABP41.08μM(IC50)體外研究ABP/PPARmodulator1(Compound27)hassuperiorbindingcapacityonPPARs(Kdsof5.23μM,0.98μMand0.76μMforPPARα,PPARγandPPARδ)[1].ABP/PPARmodulator1(10mM-0.1μM)showshigheraffinityforFABP1thanitsendogenousligand,linoleicacid(LA)(Kd:5.885μMvs.LA:14.281μM)[1].體內(nèi)研究ABP/PPARmodulator1(Compound27)(5-20mg/kg,p.o.,onceadayfor4weeks)dose-dependentlyreducestheliverweight,theliverweighttobodyweightratioandNASscoreswhileinhibitinginflammation,attenuatingfibrosis,andalleviatingoxidativestressinWesterndietcombinedwithlow-doseCarbontetrachloride(HY-Y0298)(CCl4)(WD+Carbontetrachloride)inducedMASHmice,withanti-MASHefficacystrengtheningathigherdoses[1].ABP/PPARmodulator1(20mg/kg,p.o.,onceadayfor4weeks)significantlyreducesTCandhepaticTGlevelsinMASHmicemodel[1].ABP/PPARmodulator1(10mg/kg,p.o.,onceadayfor4weeks)significantlydecreasesthelevelsofliver1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemELDH,serumAST,ALT,TBA,andTBIL,anddoesnotaffecttheALPlevelinMASHmicemodel[1].AnimalModel:maleC57BL/6mice(6weeksold)weregivenahigh-sugardiet(18.9g/Lglucoseand23.1g/Lfructose)andahigh-fatfeed(41%sucrose,21.1%fat,and1.25%cholesterol)with2%CCl4oliveoil(i.p.,onceaweekfor12weeks)toinduceMASHDosage:5,10,20mg/kgAdministration:p.o.,onceadayfor4weeks,andthencollectslivertissues.Result:Dose-dependentlyreducedtheliverweight,theliverweighttobodyweightratioandNASscoresofMASHmice,withitsanti-MASHefficacysignificantlyimprovingasthedosageincreased.Dose-dependentlydecreasedMPOexpressionlevelsanddownregulatedMCP-1,TNF-α,IL-1β,andIL-6mRNAexpressioninMASHmicemodel.SignificantlyreducedthelevelsofliverofTC,hepaticTGlevelsliverLDH,serumAST,ALT,TBA,andTBIL,anddidnotaffecttheALPlevelinMASHmicemodel.IncreasedthelevelsofSOD,GSH-Px,andGST,anddecreasedMDAcontent,protectingtheliverfromoxidativestressinMASHmicemodel.Significantlyreducedtheexpressionofα-SMA,TGF-βandHYPlevels,inhibitingtheactivationofhepaticstellatecellsandtheliverfibrosisinMASHmicemodel.REFERENCES[1].ChenY,etal.Discoveryofthefirst-in-classFABP/PPARmultiplemodulatorforthetreatmentofmetabolicdysfunction-associatedsteatohepatitis.EurJMedChem.2025Jul5;291:117635.McePdfHeightCaution:Producthasnotbeenfullyv