Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENCI677397Cat.No.:HY-176557CASNo.:907547-06-2分?式:C??H??N?OS分?量:457.63作?靶點:Deubiquitinase;Ferroptosis;ReactiveOxygenSpecies(ROS);GlutathionePeroxidase;Autophagy作?通路:CellCycle/DNADamage;Apoptosis;

Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κ

B;Autophagy儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性NCI677397?種USP24抑制劑。NCI677397增加脂質(zhì)ROS，激活膽醇和脂酸?物合成，通過?噬(autophagy)途徑降解ABC轉(zhuǎn)運蛋?、GPX4和DHFR，降低p-gp?平，最終導(dǎo)致耐藥性癌細(xì)胞發(fā)?鐵死亡(ferroptosis)。NCI677397可?于肺癌和腦癌的研究[1][2]。體外研究NCI677397(0-120nM,24h-7d)effectivelyreversesdrugresistanceinmultiplecancertypes:Lungcancer(T24cells)resistanttoTaxol,Braincancer(Pt3-TMZRandU87-Rcells)resistanttoTMZ(HY-17364),Nasopharyngealcancer(Hone-1-CPTRcells)resistanttoCPT(HY-16560)andColorectalcancer(HCT116-OXRcells)resistanttooxaliplatin(HY-17371)[2].NCI677397(10and20μM,4days)significantlyreducestheviabilityofTMZ-sensitiveand-resistantGBMcellsandthereisasynergisticeffectcombinedwithTMZ[1].NCI677397(0-20μM,24h)inducesautophagy,notapoptosisinbothTMZ-sensitiveandTMZ-resistantGBMcellsandA549andTaxol-resistantA549(A549-T24)cells[1].NCI677397(0-15μM,24h)inducesthebiosynthesisofcholesterolandfattyacidinU87,U87R,Pt’3,Pt’3R,A549andA549-T24cells[1].NCI677397(0-25μM,24h)inducesferroptosismediatedvialipidROSinU87,U87R,Pt’3,Pt’3RandA549-T24cells[1].NCI677397(0-25μM,24h)degradesABCG1/5/8throughtheautophagypathwayandreducesthestabilityofGPX4andDHFRinPt’3RandA549-T24cells[1].NCI677397(20μM,0-24h)induceslipidperoxidationwithin2hours,upregulatescholesterolsynthase6hourslater,andcompletestheferroptosisprocess24hourslaterinPt’3Rcells[1].1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellViabilityAssay[1]CellLine:TMZ-sensitiveGBMcells(Pt’3,A172andU87cells)andTMZ-resistantGBMcells(Pt’3R,A172RandU87Rcells)Concentration:0,10and20μMIncubationTime:4daysResult:SignificantlydecreasedtheviabilitycombinedwithTMZtreatment.WesternBlotAnalysis[1]CellLine:TMZ-sensitiveGBMcells(Pt’3,A172andU87cells)andTMZ-resistantGBMcells(Pt’3R,A172RandU87Rcells)Concentration:0,5,10,15,20μMIncubationTime:24hResult:Increasedthelevelsofautophagosome-associatedlipidatedformofLC3B(LC3B-II).DidnotincreasethelevelsofBax,anapoptoticmarker.IncreasingautophagicandapoptoticcelldeathwithTMZ.Immunofluorescence[1]CellLine:Pt’3RcellsConcentration:15μMIncubationTime:24hResult:InducedaccumulationofLC3Bspots.WesternBlotAnalysis[1]CellLine:Pt’3,Pt’3RandA549-T24cellsConcentration:0,5,10,15,20,25μMIncubationTime:24hResult:Increasedthelevelsofp-IRE1a,Bip,XBP1,p-eIF2aandCHOPinPt’3cells.IncreasedthelevelsofACSL3andACSL4inbrainandlungcancercells.Increasedhemeoxygenase-1(HO-1)andp62/SQSTM1.InducedSLC47A1upregulationinbothA549-T24andPt30Rcells.體內(nèi)研究NCI677397Z(20mg/kg,i.p.,twiceaweekfor7weeks)significantlyinhibitstumorgrowthinU87Rxenograftmicemodel[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:U87Rxenograftmodelestablishedinmalenonobesediabetic/severecombinedimmunodeficiencymice(8weeksold)[1]Dosage:20mg/kgAdministration:Intraperitonealinjection(i.p.),twiceaweekfor7weeksResult:ledtosmallertumorsizeandlowertumorweight.REFERENCES[1].ledtosmallertumorsizeandlowertumorweight.[2].WangSA,etal.USP24promotesdrugresistanceduringcancertherapy.CellDeathDiffer.2021Sep;28(9):2690-2707.McePdfHeightCaution: