Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEKeap1-Nrf2-IN-14Cat.No.:HY-151362CASNo.:1928782-31-3分?式:C??H??NO?S分?量:563.62作?靶點(diǎn):Keap1-Nrf2;ReactiveOxygenSpecies作?通路:NF-κB;Immunology/Inflammation;MetabolicEnzyme/Protease儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Keap1-Nrf2-IN-14(化合物20c)?種KEAP1-NRF2抑制劑，能有效破壞KEAP1-NRF2相互作?(IC50=75nM)，其對(duì)KEAP1的Kd值為24nM。Keap1-Nrf2-IN-14能誘導(dǎo)NRF2靶因的表達(dá)并增強(qiáng)下游的抗氧化和抗炎活性。Keap1-Nrf2-IN-14可?于氧化應(yīng)激相關(guān)炎癥的研究。IC50&TargetKEAP1-NRF275nM(IC50)體外研究Keap1-Nrf2-IN-14effectivelyactivatedNRF2-AREregulatedcytoprotectivedefensesysteminbothconcentration-andtime-dependentmannerinRAW264.7cells[1].Keap1-Nrf2-IN-14(1,10μM;12h)enhancedtheantioxidantcapacityinmacrophageRAW264.7cells[1].Keap1-Nrf2-IN-14(1,10μM;12h)attenuatesLPS-inducedproductionofinflammationfactorsinRAW264.7cells[1].Keap1-Nrf2-IN-14showshighmetabolicstability(inco-incubationwithratlivermicrosomeswithhalf-lifeof10.5h),andhavenoCYPinhibitionon1A2,2C9,2C19,2D6and3A4whenat10μM.CellViabilityAssay[1]CellLine:RAW264.7cells(LPS-stimulated)Concentration:10μMIncubationTime:12hResult:SignificantlyreducedROSgenerationtonearlynormallevel.1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellViabilityAssay[1]CellLine:RAW264.7cells(LPS-stimulated)Concentration:1,10μMIncubationTime:12hResult:NotablyrestoredtheSODandGSH-Pxlevels.MarkedlyattenuatedthelevelsoftheinflammatoryfactorsIL-1b,IL-6,TNF-aandNO(inducedbyLPS)inaconcentration-dependentmanner,andwhenat10μM,almostreducedthesecytokinestothebasallevel.RT-PCR[1]CellLine:RAW264.7cellsConcentration:0.1,1,5,10μMIncubationTime:12hResult:StronglyincreasedthetranscriptionofNRF2regulatedgenesinRAW264.7cellsataconcentration-dependentmanner.WesternBlotAnalysis[1]CellLine:RAW264.7cellsConcentration:10μMIncubationTime:1,2,4,8,16,24hResult:LedtonucleartranslocationofNRF2beganwithin2h,maximizedat8handsubsequentlydeclinedafter16h.InducedNRF2,HO-1,NQO-1andGCLMproteinexpressioninatime-dependentmanner.體內(nèi)研究Keap1-Nrf2-IN-14(10mg/kg;i.p.;singledailyfor3days)reducestheLPS-inducedproductionoftheproinflammatoryfactorsinvivo[1].Keap1-Nrf2-IN-14(1mg/kg;i.v.;single)showshalf-lifeof1.72hinvivo[1].AnimalModel:FemaleC57BL/6mice(18-22g;LPS-inducedinflammationmodel)[1].Dosage:10mg/kgAdministration:Intraperitonealinjection;singledailyfor3days.Result:DiminishedLPS-inducedinflammatoryresponseinvivo.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:FemaleC57BL/6mice(18-22g;LPS-inducedinflammationmodel)[1].Dosage:1mg/kgAdministration:Intravenousinjection;single.Result:Ledtohalf-lifeof1.72h.REFERENCES[1].LuMC,etal.Discoveryof2-oxy-2-phenylaceticacidsubstitutednaphthalenesulfonamidederivativesaspotentKEAP1-NRF2protein-proteininteractioninhibitorsforinflammatoryconditions.EuropeanJournalofMedicinalChemistry,2020,207:112734.McePdfHeightCaution:Producthasnotbeenfullyva