Keap1-Nrf2-IN-14-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEKeap1-Nrf2-IN-14Cat.No.:HY-151362CASNo.:1928782-31-3分⼦式:C₃₀H₂₉NO₈S分⼦量:563.62作⽤靶点:Keap1-Nrf2;ReactiveOxygenSpecies作⽤通路:NF-κB;Immunology/Inflammation;MetabolicEnzyme/Protease储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Keap1-Nrf2-IN-14(化合物20c)⼀种KEAP1-NRF2抑制剂，能有效破坏KEAP1-NRF2相互作⽤(IC50=75nM)，其对KEAP1的Kd值为24nM。Keap1-Nrf2-IN-14能诱导NRF2靶因的表达并增强下游的抗氧化和抗炎活性。Keap1-Nrf2-IN-14可⽤于氧化应激相关炎症的研究。IC50&TargetKEAP1-NRF275nM(IC50)体外研究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—您⾝边的抑制剂⼤师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.体内研究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—您⾝边的抑制剂⼤师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