PDE-TRPA1-CHIT1-IN-1-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPDE/TRPA1/CHIT1-IN-1Cat.No.:HY-179503分⼦式:C₂₈H₃₃N₇O₅分⼦量:547.61作⽤靶点:Phosphodiesterase(PDE);TRPChannel;NOD-likeReceptor(NLR);NF-κB;TNFReceptor;InterleukinRelated作⽤通路:MetabolicEnzyme/Protease;MembraneTransporter/IonChannel;NeuronalSignaling;Immunology/Inflammation;NF-κB;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PDE/TRPA1/CHIT1-IN-1⼀种PDEs、TRPA1及hCHIT1(KD值为37.7μM)抑制剂。PDE/TRPA1/CHIT1-IN-1⼀种⼴谱PDE抑制剂，可强效作⽤于包括PDE4B、PDE7A、PDE3A和PDE8A在内的关键亚型其IC50值分别为15.54，15.15，8.39和16.46μM。PDE/TRPA1/CHIT1-IN-1能够抑制NLRP3炎症⼩体激活并阻断NF-κB磷酸化，从⽽下调体内促炎因(TNF-α和IL-6)的表达。PDE/TRPA1/CHIT1-IN-1可⽤于慢性阻塞性肺疾病及相关炎症性肺病的研究[1]。IC50&TargetPDE4BPDE7APDE3APDE8A15.54μM(IC50)15.15μM(IC50)8.39μM(IC50)16.64μM(IC50)PDE1BPDE2APDE4DPDE5A54.47μM(IC50)79.61μM(IC50)130.50μM(IC50)26.86μM(IC50)PDE10A36.13μM(IC50)体外研究PDE/TRPA1/CHIT1-IN-1(compound39)(10μM,1h)possessesanti-inflammatoryactivityinLipopolysaccharides(LPS)(HY-D1056)-stimulatedRAW264.7macrophages[1].PDE/TRPA1/CHIT1-IN-1inhibitsPDE1B,PDE2A,PDE4B,PED7A,PDE3A,PDE4D,PDE5A,PDE8AandPDE10AwithIC50sof54.47,79.61,15.54,15.15,8.39,130.50,26.86,16.46and36.13μM,respectively[1].PDE/TRPA1/CHIT1-IN-1(1-50μM,1h)inhibitsbronchialsmoothmusclecell(BSMC)hyperplasiaandhypertrophy,reducesextracellularmatrix(ECM)componentsecretioninbothBSMCandhumanlungfibroblastcellline(MRC-5)cells,andinhibitsthefibroblast-to-myofibroblasttransition[1].1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEPDE/TRPA1/CHIT1-IN-1showsbronchorelaxanteffectswithIC50valuesof1.56μM,andmaximalrelaxationofprecontractedtrachealsegmentswiththemaximalrelaxationof100%inrattrachealsegments[1].PDE/TRPA1/CHIT1-IN-1possesseshighmetabolicstability(t₁/₂=53.42min,Clint=32.43μL/min/mg),negligiblehepatocytotoxicity(IC50=34.70μMinHepG2cells),andmediummembranepermeability(logPe=-5.305)[1].ELISAAssay[1]CellLine:LPS-stimulatedRAW264.7macrophagesConcentration:10μMIncubationTime:1hResult:CausedanalmosttwofoldreductioninTNF-αandIL-6levelsinLPS-inducedRAW264.7cells,loweringTNF-αconcentrationsto381.74pg/mLanddecreasingIL-6concentrationsto141.02pg/mL.CellProliferationAssay[1]CellLine:FBSinduced-MRC-5,FBSinduced-BSMC,TGF-βinduced-MRC-5andTGF-βinduced-BSMCConcentration:1,10and50μMIncubationTime:1hResult:ReducedBSMCandMRC-5proliferationby38%and32%ataconcentrationof10μM.ReducedTGF-β-inducedexpressionofCOL1A1andFN1genesinbothcelllines.DecreasedTGF-β-inducedACTA2expressioninBSMCsbyalmosta3-fold.ReduceTGF-β-inducedACTA2expressioninlungfibroblasts.体内研究PDE/TRPA1/CHIT1-IN-1(compound39)(25mg/kg,i.p.,oncedaily,for2weeks)showsanti-inflammatorypropertiesandregulatestheNLRP3inflammasomeinelastase-inducedpulmonaryemphysemamodel[1].AnimalModel:PPE(HY-B2118)(intranasally,i.n.onceaweekfor4week)induced-Balb/cmalemice(8-10weeks,23-25g)[1]Dosage:25mg/kgAdministration:i.p.,oncedaily;for2weeksResult:Protectedagainstelastase-inducedemphysemawithameanlinearintercept(MLI)valuesof50.36μM.Amelioratedtheelastase-inducedincreaseintotalinflammatorycellsininbronchoalveolarlavagefluid(BALF).ReducedthetotalnumberofallinflammatorycellsinBALFcollectedfromthePPE-2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEinducedmodel.ActedasarelativelystronginhibitorofPDE7AandPDE3A,aswellasaTRPA1antagonist.ReducedthePPE-inducedtranscriptlevelsofkeyinflammatorygenesinlunghomogenatestocontrollevels.DecreaseinTnfa,Cxcl2,Il6,andIl1bexpression.LimitedthelevelsofNLRP3inflammasomecomponentsandconsequentlyreducedtheactivationofNLRP3inflammasomecomponents.ReducedthePPE-inducedlevelofcleavedcaspase-1,whichmayhaveinhibitedtheformationofinterleukin1β(IL-1β),ahallmarkcytokineofNLRP3inflammasomeactivation.ReducedNF-κBphosphorylation,aswellastheexpressionofvariousproinflammatorygenes,includingTnfa,Cxcl2,Il6,andIl1b.REFERENCES[1].Chłoń-RzepaG,eral.Purine-2,6-dione-basedmultitarget-directedligandsinhibitingPDE/TRPA1/CHIT1asanewapproachforthetreatmentofCOPD.BioorgChem.2025D