MS479-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEMS479Cat.No.:HY-176035分子式: C₅₉H₈₂ClN₁₁O₅S分子量: 1092.87作用靶点: PROTACs;EpigeneticReaderDomain作用通路: PROTAC;Epigenetics储存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性MS479是一种BRD4PROTAC降解剂。MS479与BRD4-BD2和GLP具有高亲和力结合(BRD4-BD2：Kd=200nM；GLP：Kd=306nM)。MS479可以降低BRD4短异构体的蛋白水平。MS479通过直接结合其底物GLP作为桥接蛋白来募集E3连接酶SPOP。MS479可用于抑制结直肠癌细胞的增殖。(粉色：BRD4配体(HY-78695)；蓝色：GLP配体(HY-176036)；黑色：连接子(HY-176037)；GLP配体+连接子：HY-176038)[1]。体外研究MS479(Compound9)(0.5-5μM,24h)showsthebestdegradationofBRD4(S)(>50%degradationat5μM)inHT29cellline[1].MS479(0.156-10μM,24h)showsrelativelyweakeffectontheBRD4(L)proteinlevel(DC50=13.2μM),withapproximately50%degradationat10μMinHT29cellline[1].MS479(1-10μM,24h)regulatestheBRD4proteinlevelthroughapost-translationalmechanisminHT29cellline[1].MS479(5μM,24h)suggeststhedegradationofBRD4(S)isdependentonBRD4,GLP,SPOP,andUPSengagementinHT29cellline[1].MS479(0.021-10μM,72h)displaysasignificantantiproliferativeeffect(GI50=4.5μM)inaconcentration-dependentmannerinHT29cellsbutnotcytotoxictonormalcells[1].WesternBlotAnalysis[1]CellLine:HT29Concentration:1-10μMIncubationTime:2-72hResult:ObserveddegradationofBRD4(S)at16handpersistedupto72h.1/2 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemERequiredlongertime(48horlonger)todegradeBRD4(L),BRD3,andBRD2effectively.Reducedc-Mycproteinlevelsharplyafter2handcompletelyabolishedat16h.WesternBlotAnalysis[1]CellLine:Biotin-MS479(20or100μM),parentBRD4ligand(JQ1(HY-13030),1μM),parentGLPligand(MS1262,1μM)oraneddylationinhibitor(MLN4924(HY-70062),1μM)pre-treatedHT29celllinesConcentration:5μMIncubationTime:24hResult:RescuedBRD4(S)degradationbypretreatmentofHT29cells.InducedBRD4degradationinHT29cells,butthenegativecontrols(MS479N1andMS479N2)didnot.ShowedBRD4(S),BRD4(L),andGLPallcoelutedwithSPOPinthepresenceofBiotinMS479,suggestingMS479indeedinducestheinteractionbetweenBRD4andtheGLP-SPOPcomplex.REFERENCESDengZ,etal.,HarnessingtheSPOPE3UbiquitinLigaseviaaBridgedProteolysisTargetingChimera(PROTAC)StrategyforTargetedProteinDegradation.JMedChem.2025Apr24;68(8):8634-8647.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.For