ZLMT-72-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEZLMT-72Cat.No.:HY-179633分⼦式:C₂₉H₃₂FN₅O分⼦量:485.6作⽤靶点:CDK;Apoptosis;DNA/RNASynthesis;Bcl-2Family;IAP作⽤通路:CellCycle/DNADamage;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性ZLMT-72⼀种⼝服有效的双重CDK2和CDK9抑制剂，其IC50值分别为0.741nM和1.03nM。ZLMT-72在激酶谱分析和胆碱酯酶抑制活性⽅均表现出良好的选择性。ZLMT-72对结直肠癌(CRC)细胞系HCT116具有显著的抗增殖作⽤(GI50<0.1nM)。ZLMT-72通过抑制视⽹膜母细胞瘤蛋⽩和RNA聚合酶II(RNApolymeraseII)的磷酸化诱导细胞凋亡(apoptosis)，从⽽下调抗凋亡蛋⽩(Mcl-1和XIAP)的表达。ZLMT-72可⽤于结直肠癌(CRC)的研究。IC50&TargetCDK2/CycA2CDK9/CycT1Mcl-1XIAP0.741(IC50)1.03(IC50)体外研究ZLMT-72(1-10nM;10days)completelysuppressescolonyformationinHCT116cells[1].ZLMT-72(1-10nM;72hours)demonstratespotentantiproliferativeeffectsinHCT116cells[1].ZLMT-72(1-10nM;48hours)inducessignificantapoptosisinHCT116cells[1].ZLMT-72(1-10nM;24hours)significantlyinhibitsHCT116cellmigration[1].ZLMT-72(1-10nM;48hours)inhibitsCDK2/9andreducesantiapoptoticproteinexpressioninHCT116cells[1].CellProliferationAssay[1]CellLine:HCT116cellsConcentration:1nM,3.3nM,10nMIncubationTime:72hoursResult:Exhibitedpotentantiproliferativeeffects,withGI50values<0.1nM.Thecompound1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEsignificantlyinhibitedcellproliferation.CellProliferationAssay[1]CellLine:HCT116cellsConcentration:1nM,3.3nM,10nMIncubationTime:10daysResult:CompletelysuppressedcolonyformationinHCT116cellsat10nM,demonstratingstrongantiproliferativeactivity.ApoptosisAnalysis[1]CellLine:HCT116cellsConcentration:10nM,3.3nM,1nMIncubationTime:48hoursResult:Inducedapoptosisin30.19%ofHCT116cellsat10nM,with23.3%early-stageand6.89%late-stageapoptosis.CellMigrationAssay[1]CellLine:HCT116cellsConcentration:1nM,3.3nM,10nMIncubationTime:24hoursResult:SignificantlyinhibitedHCT116cellmigrationat10nMand3.3nM,withareducedmigrationrate.WesternBlotAnalysis[1]CellLine:HCT116cellsConcentration:10nM,3.3nM,1nMIncubationTime:48hoursResult:SignificantlydownregulatedthelevelsofphosphorylatedRb(p-Rb)andinhibitedthephosphorylationofRNApolymeraseIIattheSer2site,indicatingCDK2/9inhibition.Alsoreducedtheexpressionofantiapoptoticproteins(MCL-1andXIAP).体内研究ZLMT-72(1.1-10mg/kg,oral,twicedailyfor14days)exhibitsrobustantitumorefficacyinHCT116xenograft2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEmodelswithfavorablesafetyinsubcutaneousandorthotopictumormodels[1].AnimalModel:Balb/cnudemicebearingHCT116cells(subcutaneousandorthotopicxenografttumormodels)[1]Dosage:10mg/kg,3.3mg/kg,1.1mg/kgAdministration:Oral,oral,twicedaily,for14daysResult:Tumorgrowthwassignificantlyinhibitedinbothsubcutaneousandorthotopicmodels.At10mg/kg,tumorgrowthinhibition(TGI)was50.6%insubcutaneousmodelsand84.3%inorthotopicmodels.RevealedasignificantredreductioninKi67-positiveandCDK20-positivecells.Tumorweightandvolumeweresignificantlyreduced,andnosignificanttoxicitywasobserved.REFERENCES[1].WuL,etal.Fluorocyclopropyl-ContainingTacrineDerivativesasPotentandSelectiveDualCDK2/CDK9InhibitorsfortheTreatmentofColorectalCancer.JMedChem.2025;68(22):24326-24357.McePdfHeightCaution:Producthasnot