ZX-29-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEZX-29Cat.No.:HY-135887CASNo.:2254805-62-2分⼦式:C₂₃H₂₈ClN₇O₃S分⼦量:518.03作⽤靶点:ALK;Apoptosis;Autophagy作⽤通路:ProteinTyrosineKinase/RTK;Apoptosis;Autophagy储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性ZX-29⼀种有效的选择性的ALK抑制剂，对ALK，ALKL1196M和ALKG1202R的IC50分别为2.1nM，1.3nM和3.9nM，但对EGFR⽆活性。ZX-29通过诱导内质⽹应激来诱导细胞凋亡(apoptosis)，并克服了由ALK突变引起的细胞抗性。ZX-29还可诱导保护性⾃噬(autophagy)并具有抗肿瘤作⽤。IC50&TargetIC50:2.1nM(ALK),1.3nM(ALKL1196M)and3.9nM(ALKG1202R)[1]体外研究ZX-29(0-81nM;24-72hours;NCI-H2228cells)treatmentleadstoatime-anddose-dependentdecreaseinNCI-H2228cellviability[1].ZX-29(10nM;24hours;NCI-H2228cells)treatmentcausestypicalsignsofautophagyandtheformationofautophagosomes.ZX-29enhancestheexpressionlevelofLC3andBeclin1[1].ZX-29(10nM;0-48hours;NCI-H2228cells)inhibitstheproliferationofNCI-H2228cellsandarreststhecellsinG1phase[1].ZX-29(10-40nM;24-48hours;NCI-H2228cells)treatmentinducesapoptosisofNCI-H2228cells.ZX-29dose-dependentlyupregulatestheexpressionlevelsofproapoptoticproteinBax,increasestheproductionofactivatedformsofcaspase3,anddownregulatestheexpressionlevelofantiapoptoticproteinBcl-2[1].ZX-29(30-300nM;24hours;NCI-H2228cells)treatmentsignificantlydown-regulatestheexpressionofp-ALKanditsdownstreamsignalingproteins,includingp-Aktandp-STAT3,inadose-dependentmanner[1].ZX-29(20nM;0-48hours;NCI-H2228cells)treatmentsignificantlyincreasesthemRNAlevelofCHOP[1].ZX-29dose-dependentlyinhibitscolonyformationofNCI-H2228cells.WithanincreaseinZX-29concentration,thecelldensitydecreasedgradually,andthecellslosttheirnormalmorphologyandbecomesharpandslender[1].CellViabilityAssay[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:NCI-H2228cellsConcentration:0nM,1nM,3nM,9nM,10nM,27nMor81nMIncubationTime:24hours,48hoursor72hoursResult:Ledtoatime-anddose-dependentdecreaseinNCI-H2228cellviability.CellAutophagyAssay[1]CellLine:NCI-H2228cellsConcentration:10nMIncubationTime:24hoursResult:Causedtypicalsignsofautophagyandtheformationofautophagosomes.CellCycleAnalysis[1]CellLine:NCI-H2228cellsConcentration:0hour,12hours,24hoursor48hoursIncubationTime:24hoursResult:ArrestedtheNCI-H2228cellsinG1phaseinatime-dependentmanner.ApoptosisAnalysis[1]CellLine:NCI-H2228cellsConcentration:10nM,20nMor40nMIncubationTime:24hours,48hoursResult:PromotedNCI-H2228cellapoptosisinadose-dependentmanner.WesternBlotAnalysis[1]CellLine:NCI-H2228cellsConcentration:30nM,100nM,300nMIncubationTime:24hoursResult:Significantlydown-regulatedtheexpressionofp-ALKanditsdownstreamsignalingproteins,includingp-Aktandp-STAT3,inadose-dependentmanner.RT-PCR[1]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:NCI-H2228cellsConcentration:20nMIncubationTime:0hour,6hours,12hours,24hoursor48hoursResult:ThemRNAlevelofCHOPwasincreasedsignificantly.体内研究ZX-29(50mg/kg;intragastricadministration;every2days;foratotalof7times;femaleBALB/cnudemice)treatmentsuppressestumorgrowthinamousexenograftmodel[1].AnimalModel:FemaleBALB/cnudemice(4-week-old)withH2228cells[1]Dosage:50mg/kgAdministration:Intragastricadministration;every2days;foratotalof7timesResult:Showedsignificantlyattenuatedtumorgrowth.REFERENCES[1].GouW,etal.ZX-29,anovelALKinhibitor,inducesapoptosisviaERstressinALKrearrangementNSCLCcellsandovercomescellresistancecausedbyanALKmutation.BiochimBiophysActaMolCellRes.2020Mar26;1867(7):118712.McePdfHeightCau