Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEZLMT-12Cat.No.:HY-151436分?式:C??H??ClN?O分?量:479.02作?靶點:CDK;Cholinesterase(ChE);Apoptosis作?通路:CellCycle/DNADamage;NeuronalSignaling;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性ZLMT-12(compound35)他克寧衍?物，?種有效的CDK2/9抑制劑，抑制CDK9和CDK2的IC50值分別為0.002和0.011μM。ZLMT-12對AChE(IC50=19.023μM)和BuChE(IC50=2.768μM)有弱抑制作?。ZLMT-12具有低毒和抗增殖活性。ZLMT-12誘導(dǎo)細胞凋亡(apoptosis)，阻滯細胞周期在S期和G2/M期。IC50&TargetCDK9CDK2BChEAChE0.002μM(IC50)0.011μM(IC50)2.768μM(IC50)19.023μM(IC50)體外研究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?邊的抑制劑?師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.體內(nèi)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?邊的抑制劑?師www.MedChemEMcePdfHeightCaution:Producthasnotbeenfullyvalidatedformed