ZS34-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEZS34Cat.No.:HY-179622CASNo.:3106086-17-0分⼦式:C₁₈H₁₄ClN₃O₂分⼦量:339.78作⽤靶点:MethionineAdenosyltransferase(MAT)作⽤通路:Epigenetics;MetabolicEnzyme/Protease储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性ZS34⼀种⾼效、⼝服有效、且选择性的MAT2A抑制剂，IC50值为13.7nM，对hERG和UGT1A1的抑制作⽤极⼩。ZS34通过抑制SAM合成、降低SDMA⽔平和诱导DNA损伤，选择性地抑制甲硫代腺苷磷酸化酶(MTAP)缺陷型癌细胞的⽣长。ZS34在HCT116MTAP-/-异种移植⼩⿏模型中显⽰出抗肿瘤作⽤。ZS34可⽤于MTAP缺陷型癌症的研究[1]。IC50&TargetMAT2A13.7nM(IC50)体外研究ZS34(10days)inhibitstheproliferationofMTAPdeficiencycells(NCI-H838,NCI-H1437,MCF-7,MDA-MB-231andMIAPaCa-2cells)withIC50sof1.70,386,38.1,37.2,and115nM,respectively,exhibitingselectivityoverMTAPproficiencycells(A-375,AsPC-1,DU145,NCI-H460andNCI-H520)withIC50s>10000nM[1].ZS34(10days)exhibitspotentantiproliferativeeffectsagainstHCT116MTAP-nullcells(IC50=124nM)butweakactivityagainstWTHCT116cells(IC50>10000nM),demonstratingexcellentselectivityinhibitionwithaselectiveindices(SI)exceeding80.6[1].ZS34(0-10μM;96h)selectivelyinducesDNAdamageinMTAP-deficientHCT116cellsthroughMAT2Ainhibition[1].ZS34bindstotheallostericsiteoftheMAT2Adimer,forminghydrogenbondswithArg313andacoordinatedwatermolecule,andengaginginπ-πstackingwithPhe20,Trp274,andPhe18,whileitsortho-methylgroupparticipatesinaCH-πinteractionwithPhe333[1].WesternBlotAnalysis[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:HCT116(MTAP-/-)andHCT116(WT)Concentration:0,0.1,1μMIncubationTime:96hResult:Inducedadose-dependentdecreaseintheSDMAlevel,inHCT116MTAP-/-cells,butnotinHCT116WTcells.InducedamarkedincreaseinγH2AXlevels,amarkerofDNAdamage,inHCT116MTAP-/-cells,butnotinHCT116WTcells.Immunofluorescence[1]CellLine:HCT116(MTAP-/-)andHCT116(WT)Concentration:0.1,1,10μMIncubationTime:96hResult:ledtoamarkedincreaseinγH2AXlevelsinHCT116MTAP-/-cellscomparedtothecontrol,butnotinHCT116WTcells.体内研究ZS34(10and30mg/kg,p.o.,dailyfor30days)demonstratsrobustinvivoantitumorefficacyandafavorablesafetyprofileintheHCT116MTAP-/-xenograftmouesmodel[1].ZS34(400mg/kg,p.o.,singledose)showsnoobvioustoxicityinmice[1].AnimalModel:FemaleALB/cnudemicesubcutaneouslyinoculatedwithHCT116MTAP-/-cells[1]Dosage:10,30mg/kgAdministration:p.o.,dailyfor30daysResult:Significantlysuppressedtumorgrowth,withtumorgrowthinhibition(TGI)valuesof57.3%and89.0%at10and30mg/kg,respectively.Showedatendencytocausetumorregressionat30mg/kg.ReducedSAMlevelsintumors.Showednosignificantbodyweightlosscomparedtocontrol.AnimalModel:ICRmice[1]Dosage:400mg/kgAdministration:p.o.,singledoseResult:Waswelltoleratedatthishighdose.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].ZihanShi,etal.Furo[2,3-f]quinazolin-7(6H)-oneDerivativesasPotent,Selective,andOrallyBioavailableMAT2AInhibitorsforMTAP-DeficientCancerTherapy.J.Med.Chem.2025,68,24213-24231McePdfHeightCaution:Producthasnotbeenfully