PKMYT1-IN-13-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPKMYT1-IN-13Cat.No.:HY-181004分⼦式:C₂₄H₂₀N₆O₂分⼦量:424.45作⽤靶点:CDK作⽤通路:CellCycle/DNADamage储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PKMYT1-IN-13⼀种强效、⼝服活性且选择性⾼的PKMYT1抑制剂，在ADP-Glo检测中对PKMYT1的抑制作⽤IC50值⼩于10.0nM，在NanoBRET细胞实验中为19.9nM。PKMYT1-IN-13对WEE1表现出⾼度选择性。PKMYT1-IN-13在CCNE1扩增的细胞中表现出选择性抗增殖活性，⽽对野⽣型细胞响甚微。PKMYT1-IN-13在HCC1569⼩⿏异种移植模型中展现出显著的抗肿瘤活性。PKMYT1-IN-13可⽤于CCNE1扩增型癌症的研究，例如胃癌、巢癌、乳癌癌[1]。IC50&TargetCDK1PKMYT18.7nM(IC50)19.9nM(IC50)体外研究PKMYT1-IN-13(compound20)(7days)displayspotentantiproliferativeactivityinCCNE1-amplifiedcelllines(HCC1569,MKN1,OVCAR-3,AsPc-1,SW837,SW1463,andDLD-1FBXW7-/-)withIC50valuesof29.4,32.8,43.5,83.5,45.9,87.8,and328.5nM,repectively,whileshowingminimaleffectsontheirwild-typecounterparts(SK-OV-3cells(IC50=13672nM)andDLD-1parentcells(IC50>25000nM))[1].PKMYT1-IN-13(2h)inhibitsthephosphorylationofCDK1atThr14inHCC1569cells,withanIC50of8.7nM[1].PKMYT1-IN-13exhibitsfavorablesafetyprofiles(lowCYPinhibition,time-dependentinhibition(TDI),hERGactivity)andhighkinaseselectivity,achievingaselectivityscoreofS(10)=0.03acrossapanelof217kinases[1].体内研究PKMYT1-IN-13(compound20)(10and20mg/kg;p.o.;twicedailyfor26days)exhibitsdose-dependentantitumorefficacyintheHCC1569xenograftmousemodel[1].AnimalModel:FemaleNOD-SCID(6-8weeksold)subcutaneoouslyimplantedwithHCC1569cells[1]1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDosage:10;20mg/kgAdministration:p.o.;twicedailyfor26daysResult:Induceddose-dependenttumorgrowthinhibition(TGI)with66%TGIat10mg/kgand86%TGIat20mg/kg.ShowedsustainedinhibitionofpCDK1(T14)over24hourspostdose.MaintainedunboundplasmaconcentrationsabovethepCDK1(T14)IC90thresholdformostofthedosinginterval.Wastoleratedatbothdoselevels,withameanbodyweightlossof8%.REFERENCES[1].ZhuW,etal.DiscoveryofTetracyclicDerivativesasHighlyPotent,Selective,andBioavailablePKMYT1InhibitorsforCancerTherapy.JMedChem.2026;69(2):1004-1032.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearchu