LD-110-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemELD-110Cat.No.:HY-178825分子式: C₄₂H₄₁N₇O₆分子量: 739.82作用靶点: PROTACs;HistoneDemethylase;Apoptosis作用通路: PROTAC;Epigenetics;Apoptosis储存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性LD-110是一种高效的PROTAC降解剂，靶向LSD1(DC50=0.44μM)。LD-110以泛素-蛋白酶体依赖的方式促进LSD1降解并提高H3K4二甲基化水平。LD-110通过诱导细胞凋亡(apoptosis)抑制多种食管鳞状细胞癌(ESCC)细胞系的生长和存活。LD-110可用于食管鳞状细胞癌的研究。红色：LSD1配体(HY-178826)；蓝色：E3连接酶CRBN配体(HY-14658)；黑色：连接子(HY-N2578)[1]。体外研究LD-110(1-10μM),withalinkercontainingfourmethylenegroups,demonstratesgooddegradationactivity,achievingdegradationratesof65,70,and84%againsttheLSD1proteinatconcentrationsof1,3,and10μM,respectively[1].LD-110(0.39-12.5μM)exhibitsastrongbindingaffinitytoLSD1(Kd=6.2μM)[1].LD-110(0.1-30μM,6-72h)effectivelyanddose-dependentlydegradesLSD1protein,achievingnear-completedepletionwithin48-72hourswithDC50valuesof0.44,1.18,and1.24μMinKYSE-150,KYSE-30,andEC9706ESCCcells,respectively;thisdegradationishighlyspecificwithminimaleffectonCoREST/HDAC1/HDAC2levels,andconsequentlyleadstoapotent2to7-foldaccumulationofH3K4me2[1].LD-110(3μM,42h)-inducedLSD1degradationiseffectivelyblockedbyLSD1inhibitor(LI-1),cereblonE3ligand(Thalidomide),NAEinhibitor(MLN4924),andproteasomeinhibitor(MG132)intheKYSE-150esophagussquamouscancercells[1].LD-110(72h)effectivelysuppressesthegrowthofESCCcellswithhalf-maximalinhibitoryconcentration(IC50)valuesof3.94,3.35,and3.08μMinKYSE-150,KYSE-30,andEC9706,respectively[1].LD-110(3-10μM,10-14days)caneffectivelyinhibittheproliferationofESCCKYSE-30andEC9706cells[1].LD-110(3-10μM,48h)dose-dependentlyinducesbothearly-stageandlate-stageapoptosisandcausescleavageofPARPandcaspase-3inKYSE-30andEC9706cells[1].1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEWesternBlotAnalysis[1]CellLine:KYSE-150,KYSE-30,andEC9706ESCCcellsConcentration:10μMIncubationTime:6h,12h,24h,48h,72hResult:EffectivelyreducedtheLSD1proteinlevelsafter24-48htreatment,achievingnear-completedepletionofLSD1at48−72h,consequentlycausingtheaccumulationofH3K4me2.WesternBlotAnalysis[1]CellLine:KYSE-150,KYSE-30,andEC9706ESCCcellsConcentration:0.1μM,0.3μM,1μM,3μM,10μM,30μMIncubationTime:48hResult:Causedthedose-dependentdegradationofLSD1withDC50valuesof0.44,1.18,and1.24μMintheKYSE-150,KYSE-30,andEC9706,respectively.CausedaccumulationofH3K4me2,whichalsooccurredinadose-dependentmanner.CellProliferationAssay[1]CellLine:KYSE-30,EC9706ESCCcellsConcentration:3μM,10μMIncubationTime:10-14daysResult:SignificantlyreducedthenumberofclonesformedinESCCKYSE-30andEC9706cellsinadose-dependentmanner.ApoptosisAnalysis[1]CellLine:KYSE-30cells,EC9706ESCCcellsConcentration:3μM,10μMIncubationTime:48hResult:Inducedbothearly-stageandlate-stageapoptosisinadose-dependentmanner.体内研究LD-110(30mg/kg,100mg/kg,i.p.,oncedailyfor24days)exhibitspotentdose-dependentantitumoractivityintheKYSE-150xenograftmicemodelwithoutcausingsignificanttoxicity[1].2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEAnimalModel:5×106KYSE-150cellswereinjectedintobothflanksofthemaleBALB/cnudemice[1].Dosage:30mg/kg,100mg/kgAdministration:I.p.,oncedailyfor24daysResult:Dose-dependentlyinhibitedthetumorgrowthatboth30and100mg/kgviaintraperitonealadministrationwithoutanyeffectonbodyweight.Atadoseof100mg/kgalsoeffectivelyreducedthelevelsofLSD1proteininthetumortissuesharvestedandcollectedattheendofthestudywithoutcausinganymorphologicalchangesofmajororgans,includingheart,liver,spleen,lung,andkidney.REFERENCESZhuoJ,etal.DiscoveryofLD-110asanEffectiveLSD1PROTACDegraderfortheTreatmentofEsophagusSquamousCancer.JMedChem.2025Oct23;68(20):21860-21877.Mce