F44-A13-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEF44-A13Cat.No.:HY-163436CASNo.:1338190-14-9分子式:C₂₈H₄₀N₄O₅S分子量:544.71作用靶点:FXR;CytochromeP450;RAR/RXR;PPAR;ROR作用通路:MetabolicEnzyme/Protease;VitaminDRelated/NuclearReceptor;CellCycle/DNADamage储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性F44-A13是一种具有口服活性、高选择性的farnesoidXreceptor(FXR)拮抗剂，IC50值为1.1μM。F44-A13通过诱导CYP7A1的表达，能优化胆固醇代谢并降低其活性。F44-A13能降低小鼠模型中胆固醇、甘油三酯和低密度脂蛋白胆固醇(LDL-C)的水平。F44-A13可用于伴有脂质紊乱的代谢性疾病的研究[1]。IC50&TargetPPARαPPARβRXRαRXRβRXRγRXRαRXRβRXRγRORγ体外研究F44-A13demonstrateshighselectivitytowardsvariousnuclearreceptors,includingretinoicacidreceptorα/β/γ(RARα/β/γ),retinoidXreceptorα/β/γ(RXRα/β/γ),pregnaneXreceptor(PXR),peroxisomeproliferators-activatedreceptorsα/β(PPARα/β),thyroidhormonereceptorβ(THRβ),andretinoicacidreceptor-relatedorphanreceptorsγ(RORγ)[1].F44-A13(50μM,24h)inhibitesFXRtranscriptionalactivityinadose-dependentmannerinthepresenceof50μMCDCA(HY-76847)withanIC50valueof3.0μM.F44-A13isalow-toxicity,highlyselectiveFXRantagonist[1].F44-A13(F44-A13:3,10,30μM;CDCA:100μM;24hours)canimprovecholesterolmetabolismandreducecholesterolactivitybyinducingtheexpressionofCYP7A1.F44-A13candecreasetheexpressionlevelofShpandBsep,andincreasetheexpressionlevelofCYP7A1[1].CellViabilityAssay[1]1/2 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemECellLine:HepG2,HEK293AcellsConcentration:100μMIncubationTime:24hResult:WasnotcytotoxictoHepG2andHEK293AcellsRT-PCR[1]CellLine:HepG2cellsConcentration:F44-A13:3,10,30μM;CDCA:100μMIncubationTime:24hResult:WasabletoreversetheregulationofFXRdownstreamtargetgenesShp,BsepandCyp7a1byCDCAinadose-dependentmanner.DecreasedtheexpressionlevelofShpandBsep,andincreasedtheexpressionlevelofCyp7a1.体内研究F44-A13(20,40mg/kg;Oralgavage(p.o.)andIntraperitonealinjection(i.p.);4days)effectivelyreducesthelevelsofTC,TGandLDL-CinaC57BL/6micemodel[1].AnimalModel:C57BL/6mice[1]Dosage:20,40mg/kgAdministration:Intraperitonealinjection(i.p.)andOralgavage(p.o.);4daysResult:IntraperitonealinjectionsignificantlyreducedTClevelsbymorethan28%,andoraladministrationsignificantlyreducedTClevelsinadose-dependentmanner.ReducedTGlevelsbymorethan30%atboth20and40mg/kgorally,whileintraperitonealinjectiondidnotsignificantlyreduceTGlevels.Oraldosesof20and40mg/kgwereeffectiveinreducingLDL-Clevelsby12%and23%,andintraperitonealinjectionsby38%.REFERENCESDouX,etal.DiscoveryofnovelandselectivefarnesoidXreceptorantagoniststhroughstructure-basedvirtualscreening,preliminarystructure-activityrelationshipstudy,andbiologicalevaluation.EurJMedChem.2024;269:116323.McePdfHeightCaution:Producthasnotbeenfullyvalidatedform