WS-384-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEWS-384Cat.No.:HY-161470分子式:C₁₈H₂₁BrClN₉S₂分子量:542.91作用靶点:HistoneDemethylase;E1/E2/E3Enzyme;DNA/RNASynthesis;Caspase;Apoptosis作用通路:Epigenetics;MetabolicEnzyme/Protease;CellCycle/DNADamage;Apoptosis储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性WS-384是一种具有口服活性的双LSD1和DCN1-UBC12蛋白-蛋白相互作用抑制剂，IC50值分别为338.79nM和14.81nM。WS-384具有抗癌活性，可以引起细胞周期阻滞、DNA损伤和诱导细胞凋亡(apoptosis)。WS-38可以用于非小细胞肺癌(NSCLC)的研究[1]。IC50&TargetIC50:338.79nM(LSD1)[1].IC50:14.81nM(DCN1-UBC12Protein-proteininteraction)[1].体外研究WS-384(1-32μM;24-72h)inhibitsthegrowthofA549andH1975cellsinatime-anddose-dependentmanner,withanIC50rangingfrom2.15to6.67μM,demonstratinganticanceractivity[1].WS-384(1-8μM;48h)enhancestheexpressionlevelsofp21geneandproteininA549andH1975cellsbyinhibitingtheneddylationofcullin1andreducingtheH3K4demethylationattheCDKN1Apromoter,thusinducingcellcyclearrestattheG2/Mphaseandapoptosis.Additionally,WS-384(1-8μM;48h)canalsocauseDNAdamage[1].ApoptosisAnalysis[1]CellLine:A549,H1975Concentration:1μM,2μM,4μM,8μM(A549);0.5μM,1μM,2μM,4μM(H1975)IncubationTime:48hResult:Increasedtheapoptosisrateinaconcentration-dependentmanner,withtheapoptosis1/2 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemErateofA549cellsreaching44.9%ataconcentrationof8μMandtheapoptosisrateofH1975cellsreaching36.42%ataconcentrationof4μM.WesternBlotAnalysis[1]CellLine:A549,H1975Concentration:2μM,4μM,8μM(A549);1μM,2μM,4μM(H1975)IncubationTime:48hResult:Blockedtheneddylationofcullin1andcullin3buthadnoeffectontheneddylationofothercullinmembers(cullin2,cullin4A,andcullin5).Increasedtheproteinsexpressionofcleavedcaspase3,cleavedcaspase7,cleavedcaspase9,andcleavedPARP.Decreasedtheproteinexpressionofp-CDC2,cyclinB1.CDK4andCDK6.Increasedtheproteinexpressionγ-H2AX(amarkerproteinofDNAdamage).体内研究WS-384(25-50mg/kg;p.o.;oncedailyfor36consecutivedays)effectivelyinhibitsthegrowthofNSCLCtumorsintheBALB/cnudemousexenograftmodelwithlowtoxicity[1].AnimalModel:BALB/cnudemicexenograftmodel[1].Dosage:25mg/kg;50mg/kg;Administration:Oralgavage(p.o.);Oncedailyfor36consecutivedaysResult:Significantlyreducedtumorweightandvolumeinmiceinthe50mg/kggroup.Hadnosignificanttoxiceffectsontheheart,liver,spleen,lungs,andkidneys.REFERENCESLiA,etal.DiscoveryofWS-384,afirst-in-classdualLSD1andDCN1-UBC12protein-proteininteractioninhibitorforthetreatmentofnon-smallcelllungcancer.BiomedPharmacother.2024;173:116240.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical