Phosphodiesterase-IN-5-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPhosphodiesterase-IN-5Cat.No.:HY-179645分⼦式:C₂₆H₂₆FN₇O分⼦量:471.53作⽤靶点:Phosphodiesterase(PDE);PKA;InterleukinRelated;TNFReceptor;Collagen作⽤通路:MetabolicEnzyme/Protease;StemCell/Wnt;TGF-beta/Smad;Immunology/Inflammation;Apoptosis;Cytoskeleton储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Phosphodiesterase-IN-5⼀种强效、⼝服有效的选择性磷酸⼆酯酶10A(PDE10A)抑制剂，IC50值为6.2nM。Phosphodiesterase-IN-5对其他PDE亚型表现出1612倍以上的选择性。Phosphodiesterase-IN-5通过阻断cAMP/PKA/CREB信号通路，抑制肌成纤维细胞分化，在Bleomycin(BLM)(HY-108345)诱导的⼩⿏肺纤维化(PF)模型中表现出显著的抗纤维化作⽤。Phosphodiesterase-IN-5可⽤于肺纤维化的研究[1]。IC50&TargetPDE10A6.2nM(IC50)体外研究Phosphodiesterase-IN-5(compoundQC-3)(5-20μM;48h)exhibitsantifibroticactivityinTGF-β1(HY-163536)-stimulatedMRC-5cellsviaactivationofthecAMP/PKA/CREBpathway,whichinhibitsmyofibroblastdifferentiationandECMdeposition[1].Phosphodiesterase-IN-5bindsthecatalyticdomainofPDE10A,forminghydrogenbondswithGln726andhydrophobicinteractionswithIle692,whilethe6-FsubstituentenableshalogenbondingwithAsp674viaawatermolecule[1].CellViabilityAssayWesternBlotAnalysisCellProliferationAssayApoptosisAnalysisCellCytotoxicityAssayCellCycleAnalysisRT-PCRCellAutophagyAssayImmunofluorescenceCellDifferentiationAssayCell[1]CellLine:MRC-5cellsConcentration:3.125,6.25,12.5,25,50,100,200μMIncubationTime:48h1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:ShowednocytotoxicinMRC-5cellsatconcentrationsupto200μM.WesternBlotAnalysis[1]CellLine:TGF-β1-stimulatedMRC-5cellsConcentration:5,10,20μMIncubationTime:48hResult:Demonstratedconcentration-dependentreductionsinFN,COL-I,andα-SMAproteinexpression.体内研究Phosphodiesterase-IN-5(10mg/kg,i.g.,dailyfor21days)exhibtspotentantifibroticefficacyinaBLM-inducedmurinemodelofPFbyblockingmyofibroblastdifferentiationviathecAMP/PKA/CREBsignalingpathway[1].AnimalModel:MaleC57BL/6mice(7-9weeksold,20-24g)inducedbyBLM[1]Dosage:2.5,5,10mg/kgAdministration:i.g.;dailyfor21daysResult:Dose-dependentlyreversedBLM-inducedchangesinPenh,endexpiratorypause(EEP),relaxationtime(RT),andfrequency(f),nearlyrestoringthemtonormallevels.MitigatedBLM-inducedbodyweightlossandelevatedlungcoefficientinadose-dependentmanner.ReducedIL-6andTGF-βlevelsinbronchoalveolarlavagefluid(BALF),andrestoredpulmonarycAMPlevels.MarkedlyreducedBLM-inducedincreasesinIL-6andTGF-βlevelsinBALF,withthemospronouncedinhibitionobservedatthe10mg/kgdose.RestoredpulmonarycAMPlevels.Improvedpulmonarymorphology.Effectivelyreducedthelevelofalveolarwallthickening,inflammatorycellinfiltration,andcollagendeposition.Showedadose-dependentreductioninfibroticlesions.SignificantlysuppressedtheBLM-inducedoverexpressionoffibroticmarkerssuchasFN,COL-I,andα-SMA,withthemostpronouncedeffectobservedatadoseof10mg/kg.REFERENCES[1].ZhangF,etal.Structure-BasedOptimizationofImidazopyridineDerivativesasSelectiveandOrallyBioavailablePhosphodiesterase10AInhibitorswithReducedBlood-BrainBarrierPenetrationfortheTreatmentofIdiopathicPulmonaryFibrosis.JMedChem.2025;68(23):25290-25306.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMcePdfHeightCaution:Producthasnot