BMS-986339-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBMS-986339Cat.No.:HY-150787CASNo.:2477873-64-4分⼦式:C₃₅H₄₁F₄N₃O₄分⼦量:643.71作⽤靶点:FXR;CytochromeP450作⽤通路:MetabolicEnzyme/Protease储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性BMS-986339⼀种具有⼝服活性的FXR激动剂。BMS-986339可与His298和ASN287残形成氢键。BMS-986339可⽤于原发性胆汁性肝硬化(PBC)、原发性硬化性胆管炎(PSC)、⾮精性脂性肝炎(NASH)，和抗纤维化研究。IC50&TargetCYP2C8CYP2C98μM(IC50)13.5μM(IC50)体外研究BMS-986339(compound32,0.1nM-10μM,24h)reducesactivationofgenesexpressingBSEP(bilesaltexportpump)inHuh-7cells,andFGF19inhepatocytes[1].BMS-986339inhibitscytochromeP450activity(IC50:8μM(CYP2C8),13.5μM(CYP2C9)),andinhibitshERGchannelinapatchclampassay(IC50:4.5μM)[1].BMS-986339inhibitstransportersOATP1B3andBSEPwithIC50valuesof1.44and1.5μM,andhUGT1A1(IC50:4.85μM)[1].体内研究BMS-986339(compound32,p.o.,10mg/kg,oncedailyfor9days)inducesFgf15production,andshowsantifibroticefficacyinmousebileductligation(BDL)model[1].BMS-986339(p.o.ori.v.,5mg/kgor1mg/kg)exhibitslowclearanceandalongeliminationhalf-lifeinmiceandrats[1].AnimalModel:Mousebileductligation(BDL)model[1]Dosage:0.3,1,3,and10mg/kg,oncedailyfor9days.1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:OraladministrationResult:InducedFgf15andSHP(smallheterodimerpartner)geneexpressiontoasimilarextentintheileum.Decreasedtheratioofhydroxyprolinetothetotalproteincontent,anddecreasedthecollagenlevels.AnimalModel:MaleC57BL6mice,maleSprague-Dawleyrat(pharmacokineticassay)[1]Dosage:5mg/kgor1mg/kgAdministration:Oraladministration,intravenousinjectionResult:PharmacokineticprofileofBMS-986339(compound32).parametermaleC57BL6micemaleSprague-Dawleyratdose(mg/kg)i.v.11dose(mg/kg)p.o.52Vss(L/kg)i.v.2.25.2AUCtotal(μM•h)i.v.16.46.6AUCtotal(μM•h)p.o.56.65.8t1/2h(i.v.)1618Fp.o.6940REFERENCES[1].SusheelJNara,etal.DiscoveryofBMS-986339,aPharmacologicallyDifferentiatedFarnesoidXReceptorAgonistfortheTreatmentofNonalcoholicSteatohepatitis.JMedChem.2022Jul14;65(13):8948-8960.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearch