NLRP3-IN-39-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENLRP3-IN-39Cat.No.:HY-161579分⼦式:C₂₁H₂₁Cl₂NO₄分⼦量:422.3作⽤靶点:NOD-likeReceptor(NLR);InterleukinRelated作⽤通路:Immunology/Inflammation储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性NLRP3-IN-39(Compound49)可以抑制NLRP3炎症⼩体的组装和活化。NLRP3-IN-39通过共价结合NLRP3蛋⽩的Cys279发挥抑制作⽤。NLRP3-IN-39可以抑制Nigericin(HY-127019)诱导的THP-1细胞中IL-1β的释放(IC50=0.29μM)[1]。IC50&TargetNLRP3IL-1β体外研究NLRP3-IN-39caninhibitNigericin-inducedIL-1βreleaseinvariouscelltypes,withIC50valuesof0.29μMinTHP-1cells,44.97nMinPBMCs,and738.8nMinBMDMs,respectively[1].NLRP3-IN-39(0-1μM;24h)effectivelyinhibitsthesecretionofinflammatorycytokinesinTHP-1cellsandBMDMswithoutaffectingtheexpressionofprecursorproteins[1].NLRP3-IN-39(0-1μM;40min)significantlyinhibitsLDHreleaseandpyroptosisinducedbyNLRP3inflammasomeactivationinTHP-1cellsandBMDMs.InLPS-primedTHP-1cells,NLRP3-IN-3showsasignificant,concentration-dependentinhibitionofnigericin-inducedIL-1βrelease[1].NLRP3-IN-39(0-1μM;40min)significantlyinhibitsLDHreleaseandpyroptosisinducedbyNLRP3inflammasomeactivationinTHP-1cellsandBMDMs.InLPS-primedTHP-1cells,NLRP3-IN-39showsasignificant,concentration-dependentinhibitionofNigericin-inducedIL-1βrelease[1].NLRP3-IN-39(1μM;24h)reducestheformationofASColigomersandASCspecksinNigericin-inducedTHP-1cells,whilethisphenomenonisnotobservedinNLRP3KOTHP-1cells[1].WesternBlotAnalysis[1]CellLine:THP-1cellsandBMDMsConcentration:0,0.25,0.5,1μM1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:24hResult:InhibitedthesecretionofIL-1βandcaspase-1inaconcentration-dependentmannerinLPS/nigericin-inducedTHP-1cellsandBMDMs,withoutsignificantlyaffectingtheexpressionofpro-IL-1β(p31),pro-caspase-1(p45),NLRP3,andASC.Immunofluorescence[1]CellLine:THP-1cellsandBMDMsConcentration:0,0.25,0.5,1μMIncubationTime:40minResult:Inhibitstheredfluorescenceofpyroptosisinaconcentration-dependentmanner,showingeffectssimilartoMCC950(HY-12815).体内研究NLRP3-IN-39(15,30mg/kg;i.p.;singledose)exhibitssignificantanti-inflammatoryeffectsinaDSS-inducedulcerativecolitismousemodel[1].NLRP3-IN-39ispreparedin5%DMSOand95%salinetoaconcentrationof3mg/mL.PharmacokineticAnalysisinC57BL/6malemice[1]RouteDose(mg/kg)AUC0−t(ng·h/mL)MRT0−t(h)Tmax(h)T1/2(h)Cmax(ng/mL)Clz/F(L/h/kg)i.p.3016.75±0.6910.98±0.560.78±0.616.83±1.171.57±0.1968.7637.40±136.40AnimalModel:DSS-inducedulcerativecolitismousemodel[1]Dosage:15,30mg/kgAdministration:i.p.;singledoseResult:Significantlyreducedtheincreasedthicknessofcolonictissue,cryptloss,gobletcelldepletion,severemucosaldamage,andsevereulcerformation.SignificantlyloweredthelevelsofIL-1βandTNF-αincolonictissueandinhibitedtheactivationofcaspase-1.REFERENCES[1].ZhaoM,etal.NovelIsoalantolactone-BasedDerivativesasPotentNLRP3InflammasomeInhibitors:Design,Synthesis,andBiologicalCharacterization.JMedChem.2024May9;67(9):7516-7538.McePdfHeight2/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECaution:Producthasnotbeen