ZLMT-12-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEZLMT-12Cat.No.:HY-151436分⼦式:C₂₆H₃₁ClN₆O分⼦量:479.02作⽤靶点:CDK;Cholinesterase(ChE);Apoptosis作⽤通路:CellCycle/DNADamage;NeuronalSignaling;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性ZLMT-12(compound35)他克宁衍⽣物，⼀种有效的CDK2/9抑制剂，抑制CDK9和CDK2的IC50值分别为0.002和0.011μM。ZLMT-12对AChE(IC50=19.023μM)和BuChE(IC50=2.768μM)有弱抑制作⽤。ZLMT-12具有低毒和抗增殖活性。ZLMT-12诱导细胞凋亡(apoptosis)，阻滞细胞周期在S期和G2/M期。IC50&TargetCDK9CDK2BChEAChE0.002μM(IC50)0.011μM(IC50)2.768μM(IC50)19.023μM(IC50)体外研究ZLMT-12(compound35;500nM;72h)hasantiproliferativeactivityincancercells[1].ZLMT-12(500nM;72h)inducesapoptosisandarreststhecellcycleintheSphaseandG2/Mphase[1].CellViabilityAssay[1]CellLine:HCT116,SW480,A549,andMCF-7cellsConcentration:500nMIncubationTime:72hoursResult:InhibitedcellproliferativewithGI50valuesof0.029,0.328,0.051,and0.109μMforHCT116,SW480,A549,andMCF-7cells,respectively.ApoptosisAnalysis[1]CellLine:HCT116cellsConcentration:10and20nM1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:48hoursResult:Increasedapoptoticcellsratefrom9.22%inthecontrolto23.77%at10nMandincreasedapoptoticcellsrateto46.2%at20nM.CellCycleAnalysis[1]CellLine:HCT116cellsConcentration:10and20nMIncubationTime:48hoursResult:IncreasedthepercentageoftheSphasefrom31.43%to42.75%(10nM)and49.38%(20nM)respectively,andthepercentageoftheG2/Mphasefrom6.39%to10.60%(10nM)and13.11%(20nM),respectively.体内研究ZLMT-12(compound35;10mg/kg;p.o.;daily,for21d)hasantitumorefficacyandinhibitstumorgrowth,withoutcausingliverharmintheHCT116xenograftmodel[1].AnimalModel:MaleBALB/cA-numicewithHCT116xenografts(18-25g,6-8weeksofage)[1]Dosage:10mg/kgAdministration:Oraladministration;daily,for21daysResult:InhibitedtumorgrowthwithGI(tumorvolumegrowthinhibition)=47.66%andTGI(tumorweightgrowthinhibition)=62.39%.Exhibitednosignificantchangesinbehaviororbodyweightinmice.Hadnoobviousliverinjury.AnimalModel:MaleSprague-Dawleyrats(240±20g)[1]Dosage:2mg/kg(i.v.)and20mg/kg(p.o.)(PharmacokineticAnalysis)Administration:Intravenousinjectionandoraladministration;onceResult:1.19Parameter2mg/kg(i.v.)20mg/kg(p.o.)T1/2(h)0.4611.77Tmax(h)0.083/td>1.00Cmax(ng/mL)20667.8AUCo-t(h*ng/mL)110302AUCo-∞(h*ng/mL)115316CL(L/h/kg)18.7Vss(L/Kg)12.6F(%)27.47REFERENCES[1].WuL,et,al.Developmentandstructure-activityrelationshipoftacrinederivativesashighlypotentCDK2/9inhibitorsforthetreatmentofcancer.EurJMedChem.2022Nov15;242:114701.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMcePdfHeightCaution:Producthasnotbeenfullyvalidatedformed