NIC-0102-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENIC-0102Cat.No.:HY-151252CASNo.:2806031-94-5分⼦式:C₂₁H₂₅BF₂N₂O₄分⼦量:418.24作⽤靶点:Proteasome作⽤通路:MetabolicEnzyme/Protease储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性NIC-0102(化合物27)⼀种⼝服有效的蛋⽩酶体抑制剂(pIC50=7.55)，能特异性地抑制NLRP3炎症⼩体激活。NIC-0102在体内对DSS诱导的溃疡性结肠炎模型显⽰出有效的抗炎作⽤。NIC-0102还能抑制前IL-1β的产⽣。IC50&Targetproteasomβ5proteasomβ2proteasomβ13.7nM(IC50)100.5nM(IC50)113.6nM(IC50)体外研究NIC-0102(7.5,15,30,60nM;1h)specificallysuppressesNLRP3inflammasomeactivationinLPS-primedJ774A.1andBMDMcells[1].NIC-0102(7.5,15,30,60nM;1h)inducespolyubiquitinationofNLRP3viainhibitionoftheproteasomeduringtheactivationstepinLPS-primedJ774A.1cells[1].NIC-0102(7.5,15,30,60nM;1h)exhibitsinhibitoryeffectsonNF-κBintheprimingstepoftheNLRP3pathwayinLPS-primedJ774A.1cells[1].NIC-0102(15,60nM;1h)blocksNLRP3-ASCinteractionandASColigomerizationinLPS-primedJ774A.1cells[1].CellViabilityAssay[1]CellLine:J774A.1andBMDMcells(LPS-primed)Concentration:7.5,15,30,60nMIncubationTime:1h1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:InhibitedthereleaseofIL-1βinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:J774A.1cells(LPS-primed)Concentration:7.5,15,30,60nMIncubationTime:1hResult:Dose-dependentlyinhibitedthereleaseofmatureIL-1βandthecaspase-1p20subunitinsupernatantsfromJ774A.1cellsbutdidnotaffectpro-IL-1β,pro-caspase-1,NLRP3,orASCincelllysates.IncreasedthepolyubiquitinatedNLRP3proteininadose-dependentmanner,andsignificantlyincreasedtheamountofc-CblandCbl-b.ShowedaninhibitoryeffectontheNF-κBsubunitp65,phosphorylatedp65,andNLRP3proteinat60nM,atwhichNF-κB-dependentTNF-αsecretionwasslightlydecreased.WesternBlotAnalysis[1]CellLine:J774A.1cells(LPS-primed)Concentration:15,60nMIncubationTime:1hResult:InhibitedtheinteractionbetweenNLRP3andASCstimulatedbyLPSandnigericin.Showedaconcentration-dependentsuppressioneffectonASColigomerization.体内研究NIC-0102(0.125,0.25,0.5mg/kg;p.o.;singleevery72hfor10days)showsstrongprotectionagainstDSS-inducedacutecolitisinmice[1].AnimalModel:MaleC57BL/6mice(6to8-week-old;DSS-inducedulcerativecolitismodel)[1].Dosage:0.125,0.25,and0.5mg/kgAdministration:Oralgavage;singleevery72hfor10days.Result:Significantlysuppressedweightandfecaloccultblood.Decreasedcoloniclengthinadose-dependentmanner.Resultedinadose-dependentreductionintissue-associatedIL-1βconcentrationandsignificantlyinhibitedpro-IL-1β.AnimalModel:MaleC57BL/6mice(6to8-week-old)[1].Dosage:0.5mg/kg(fori.v.);1mg/kg(forp.o.)2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:Intravenousinjection;Oralgavage;single.Result:1.19PharmacokineticParametersofNIC-0102inmaleC57BL/6mice[1].IV(0.5mg/kg)PO(1mg/kg)T1/2(h)4.738.36Tmax(h)0.080.25Cmax(ng/mL)376.6207.7AUC0-∞(h•ng/mL)448.8489.2MRT0-∞(h)6.14-Vz(L/kg)7.7-CL(mL/min/kg)18.8-F(%)-48.1%REFERENCES[1].WuX,etal.DiscoveryofaNovelOralProteasomeInhibitortoBlockNLRP3InflammasomeActivationwithAnti-inflammationActivity.JMedChem.2022Sep5.McePdfHeightCaution:Producthasnotbee