Topoisomerase-I-inhibitor-5-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETopoisomeraseIinhibitor5Cat.No.:HY-144774CASNo.:2513461-95-3分?式:C??H??N?O?分?量:372.46作?靶點:Topoisomerase;DNA/RNASynthesis;Apoptosis作?通路:CellCycle/DNADamage;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性TopoisomeraseIinhibitor5?種有效的拓撲異構酶(topoisomerase)抑制劑。TopoisomeraseIinhibitor5能?擾DNA，顯著抑制TopoisomeraseI活性。TopoisomeraseIinhibitor5能將細胞周期阻滯在G1期，誘導MCF-7細胞凋亡(apoptosis)。TopoisomeraseIinhibitor5具有逆轉P-gp介導的阿霉素耐藥性的效?[1]。IC50&TargetTopoisomeraseI[1]體外研究TopoisomeraseIinhibitor5(compound14)(0-50μM;48hours)exhibitsantiproliferationactivityagainstcancercelllinesandlowercytotoxicityinnormalcells[1].TopoisomeraseIinhibitor5(2-8μM;24hours)inducesMCF-7cellcyclearrestattheG1phase[1].TopoisomeraseIinhibitor5(2-8μM;48hours)increasestheapoptoticrateofMCF-7/ADRandMCF-7cells[1].TopoisomeraseIinhibitor5(1.5-6μM;24hours)increasestheexpressiondegreeofcleaved-caspase-3andcleaved-PARPinMCF-7;down-regulatesthelevelofanti-apoptoticprotein,up-regulatesthelevelsofpro-apoptoticproteinsinMCF-7/ADR[1].TopoisomeraseIinhibitor5(0.1μM;24hours)inducescellapoptosisbypromotingtheaccumulationofROSinMCF-7/ADRcell[1].TopoisomeraseIinhibitor5(10μg/ml;24hours)increasestheaccumulationoftheADRandRh123inMCF-7/ADRcells[1].TopoisomeraseIinhibitor5(5,10and20μM;24hours)reducestheexpressiondegreeofP-gpby14.95%and18.10%inMCF-7/ADRcellsat10and20μM[1].CellProliferationAssay1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:A549,HepG-2,MCF-7,MDA-MB-231,MCF-7/ADRandLO2cells[1]Concentration:0-50μMIncubationTime:48hoursResult:Exhibitedantiproliferationactivityagainstcancercelllines,withIC50sof2.39±0.23μM,4.88±0.29μM,1.32±0.14μM,7.64±0.35μMand2.42±0.14μMinA549,HepG-2,MCF-7,MDA-MB-231,MCF-7/ADR,respectively;andhaslowercytotoxicityinLO2cellswithIC50of36.52±2.36μM.CellCycleAnalysisCellLine:MCF-7[1]Concentration:2,4and8μMIncubationTime:24hoursResult:InducedMCF-7cellcyclearrestattheG1phase.ApoptosisAnalysisCellLine:MCF-7andMCF-7/ADRcells[1]Concentration:2,4and8μMIncubationTime:48hoursResult:Inducedapoptosisinadose-dependentmannerinMCF-7cells,andincreasedtheapoptoticrateofthecellsfrom2.8%to15.2%inMCF-7/ADR.WesternBlotAnalysisCellLine:MCF-7[1]Concentration:1.5,3and6μMinMCF-7;5,10,and20μMinMCF-7/ADRIncubationTime:24hoursResult:Increasedtheexpressiondegreeofcleaved-caspase-3andcleaved-PARPinMCF-7;down-regulatedthelevelofanti-apoptoticproteinbcl-2,up-regulatedthelevelsofpro-apoptoticproteinsbaxandbadinMCF-7/ADR.體內研究TopoisomeraseIinhibitor5(1mg/kgand10mg/kg;IV;everytwodays,for21days)decreasesthetumorgrowthsignificantly[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:Balb/cnudemice(injectedwith106MCF-7cellsintheleftflankfor7days)[1]Dosage:1mg/kgand10mg/kgAdministration:IV;everytwodays,for21daysResult:Decreasedthetumorgrowthsignificantlyandthetumorinhibitionratioreachedto32.4%at1mg/kgand7.2%at10mg/kg.REFERENCES[1].ZhongH,ZhaoM,WuC,ZhangJ,ChenL,SunJ.DevelopmentofoxoisoaporphinederivativeswithtopoisomeraseIinhibitionandreversalofmultidrugresistanceinbreastcancerMCF-7/ADRcells.EurJMedChem.2022;235:114300.McePdfHeightCaution:Product