Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEYZ-35Cat.No.:HY-175253分子式:C??H??N?O?S分子量:512.58作用靶點(diǎn):STAT;Apoptosis作用通路:JAK/STATSignaling;StemCell/Wnt;Apoptosis儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性YZ-35是一種STAT3抑制劑，其Ki值為0.38μM。YZ-35以高親和力直接結(jié)合STAT3，其解離常數(shù)(Kd)為190nM。YZ-35能直接抑制STAT3的雙重磷酸化(Tyr705和Ser727位點(diǎn))。YZ-35可抑制乳腺癌細(xì)胞系的菌落形成、細(xì)胞遷移，并誘導(dǎo)細(xì)胞凋亡(apoptosis)。YZ-35選擇性地抑制乳腺癌干細(xì)胞(BCSC)的自我更新能力。YZ-35在乳腺癌干細(xì)胞異種移植模型中抑制腫瘤生長。YZ-35可用于乳腺癌研究[1]。體外研究YZ-35(0.1-100μM,48h)demonstratesinhibitorypotencyagainstMDA-MB-231cells(IC50=0.63μM),MCF-7cells(IC50=0.32μM)andMCF-10Acells(IC50=34.34μM)[1].YZ-35(0-4μM,0-48h)directlyattenuatesthedualphosphorylationofSTAT3(Tyr705andSer727)toexhibitpotentanti-breastcancerefficacyefficacyinMDA-MB-231andMCF-7cells[1].YZ-35(0-6μM,24-48h)suppressescolonyformation,cellularmigration,andinducesapoptosisinMDA-MB-231andMCF-7cells[1].YZ-35(2.5-10μM,48h)reducestumorstemnessinMDA-MB-231andMCF-7cells[1].CellViabilityAssay[1]CellLine:MDA-MB-231cells,MCF-7cellsandMCF-10AcellsConcentration:0.1-100μMIncubationTime:48hResult:DemonstratedinhibitorypotencyagainstMDA-MB-231cells(IC50=0.63μM),MCF-7cells(IC50=0.32μM)andMCF-10Acells(IC50=34.34μM).WesternBlotAnalysis[1]1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECellLine:MDA-MB-231cellsandMCF-7cellsConcentration:0,1,2,3,4μMIncubationTime:0,12,24,36,48hResult:Exhibitedconcentration-andtime-dependentsuppressionofthephosphorylationofSTAT3atbothTyr705andSer727residuesinMDA-MB-231andMCF-7celllines,whilemaintainingtotalSTAT3proteinlevels.ShowednoeffectontheexpressionlevelsofSTAT1andSTAT5ortheirphosphorylation.DidnotimpactthephosphorylationofJAK2,Src,andERK.inhibitedtheexpressionofcriticalapoptosis-relatedproteins,includingCyclinD1,BCL2,BCL-xL,andSurvivin,inaconcentration-dependentmanner.CellMigrationAssay[1]CellLine:MDA-MB-231cellsandMCF-7cellsConcentration:0,1,2,3μMIncubationTime:24hResult:DecreasedthemigrationofMDA-MB-231cellsby99%.ReducedthemigrationinMCF-7cellsby72.97%.ApoptosisAnalysis[1]CellLine:MDA-MB-231cellsandMCF-7cellsConcentration:0,1,2,4,6μMIncubationTime:48hResult:Inducedprogrammedcellapoptosisinaconcentration-dependentmanner,withdifferentialresponsesobservedbetweenBRCAsubtypes:predominantlylate-stageapoptosisinMDA-MB-231cells,whilepromotingbothearlyandlate-phaseapoptoticeventsinMCF-7cells.Immunofluorescence[1]CellLine:MDA-MB-231cellsandMCF-7cellsConcentration:0,1,2,3μMIncubationTime:48hResult:InducedprogrammedcelldeathofBRCA,notablymanifestingaspronouncedchromatincondensationandnuclearfragmentation,withthemostsubstantialapoptoticphenotype2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEobservedat3μMconcentration.體內(nèi)研究YZ-35(5-10mg/kg,i.v.,oncedaily,21days)suppressestumorgrowthintheBCSCxenograftmodel[1].AnimalModel:1×107MDA-MB-21cellswereresuspendedwith100μLsalineandinjectedintotheleftflankof5-week-oldfemaleBALB/c-nudemice[1]Dosage:5,10mg/kgAdministration:i.v.oncedailyfor21daysResult:Inhibitedtumorgrowth(theTGIofhigh(10mg/kg)andlow(5mg/kg)groupswere89.98and74.13%,respectively).InhibitedSTAT3phosphorylationandsignificantlyreducedFOXM1andAURKAexpression.AugmentedtheproportionofapoptoticcellswhileconcurrentlydiminishingKi67-positiveproliferatingcellpopulationsintumortissuesrelativetovehiclecontrols.Showednosignificanttoxicitywasobservedinmajororgansincludingtheheart,liver,spleen,lung,andkidney.REFERENCESZhangZ,etal.DiscoveryofJugloneDerivativesasNovelSTAT3InhibitorswithPotentSuppressionofCancerCellStemnessagainstBreastCancer.JMedChem.2025Jul24;68(14):15085-15109.McePdfHei