Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemENrf2-IN-4Cat.No.:HY-175209CASNo.:2417486-06-5分子式:C??H??Cl?N?S分子量:426.32作用靶點:Keap1-Nrf2;Ferroptosis;ReactiveOxygenSpecies(ROS);Atg8/LC3作用通路:NF-κB;Apoptosis;Immunology/Inflammation;MetabolicEnzyme/Protease;Autophagy儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性Nrf2-IN-4是一種Nrf2抑制劑。Nrf2-IN-4通過抑制NRF2誘導(dǎo)鐵死亡(ferroptosis)。Nrf2-IN-4破壞細(xì)胞鐵穩(wěn)態(tài)，促進鐵蛋白降解，并最終觸發(fā)鐵死亡。Nrf2-IN-4通過促進鐵依賴性活性氧(ROS)產(chǎn)生和溶酶體酸化來誘導(dǎo)溶酶體激活。Nrf2-IN-4顯示出顯著的抗腫瘤效果。Nrf2-IN-4可用于乳腺癌研究[1]。體外研究Nrf2-IN-4(CompoundPhcY)(0.01-10μM,72h)exhibitsinhibitoryeffectonthecancercelllines,withIC50sof80nM(MCF-7cells),3.26μM(HepG2cells),0.90μM(T24cells),2.89μM(HCT116cells),3.27μM(L929fibroblasts)and5.36μM(HEK293humanembryonickidneycells)[1].Nrf2-IN-4(40-160nM)causesMCF-7cellstoexhibit‘ballooning’androundedcellmorphologywithvacuolatedcytosol[1].Nrf2-IN-4(40-80nM,14days)inhibitscolonyformationofMCF-7cellsinadose-dependentmanner[1].Nrf2-IN-4(80-160nM,24-48h)increaseslabileironpool(LIP)andferroptosisviainhibitionofNrf2inMCF-7cells[1].Nrf2-IN-4(80-320nM,24h)induceslysosomeactivationbypromotingiron-dependentROSproductionandlysosomalacidificationinMCF-7cells[1].Nrf2-IN-4(40-320nM,0-12h)inducesferritindegradationviaferritinophagyinMCF-7cells[1].Nrf2-IN-4(80-320nM)inducesoxidativestress,resultinginasignificantdecreaseinmitochondrialmembranepotential,aneffectthatcanbereducedbytheAcetylcysteine(N-acetylcysteine)(NAC)(HY-B0215)inMCF-7cells[1].Nrf2-IN-4(0.1-0.2μM)demonstratesapotentinhibitoryeffectonorganoidgrowth,surpassingtheefficacyofML385(HY-100523)[1].Immunofluorescence[1]CellLine:MCF-7cellsConcentration:80nM1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEIncubationTime:24hResult:IncreasedLIPandreversedtheeffectandthetheeffectwasreversedbyNrf2knockdown.CellViabilityAssay[1]CellLine:MCF-7cellsConcentration:80,160nMIncubationTime:48hResult:IncreasedcytotoxicityuponNrf2overexpression.Induceddose-dependentcytotoxicity,whichwasinhibitedbyboth1,8-Diazafluoren-9-one(DFO)(HY-D0903)andFerrostatin-1(Fer-1)(HY-100579).Immunofluorescence[1]CellLine:MCF-7cellsConcentration:80,160,320nMIncubationTime:24hResult:IncreasedcathepsinBactivityinadose-dependentmanner,whichwasinhibitedbyChloroquine(CQ)(HY-17589A)orDFO.WesternBlotAnalysis[1]CellLine:MCF-7cellsConcentration:0,3,6,9,12hIncubationTime:24hResult:Showedadose-dependentincreaseinBeclin-1,LC3-II,andATG5proteinlevels.ReducedintracellularFTHandFTLlevels,andthisreductionwasreversedbyautophagyinhibitors(BafilomycinA1(HY-100558),CQ)andtheironchelatorDFO.體內(nèi)研究Nrf2-IN-4(CompoundPhcY)(10mg/kg,i.p.,dailyfor21days)demonstratessignificantantitumorefficacyinMCF-7xenograftmice[1].AnimalModel:MCF-7cells(5×106)wereinjectedsubcutaneouslyintoeachfemaleadultathymicnudemouse[1]Dosage:10mg/kg2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEAdministration: i.p.dailyfor21daysResult: LedtothedegradationofFTHandFTL,aswellastheupregulationofP53andLC3-II.Didnotcausenotablebodyweightlossorotherobservableadverseeffectsinmice.REFERENCESMengX,etal.Discoveryofnovelthiazolylhydrazonederivativesaspotentanti-canceragentsinducingferroptosisviadirectNRF2inhibition.EurJMedChem.2025Jun28;297:117912.McePdfHeightCaution:Producth