NSD2-IN-6-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENSD2-IN-6Cat.No.:HY-180553分⼦式:C₂₅H₂₆F₄N₈O₂分⼦量:546.52作⽤靶点:HistoneMethyltransferase作⽤通路:Epigenetics储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性NSD2-IN-6⼀种选择性NSD2抑制剂，对NSD2和NSD1的IC50分别为3.8nM和274nM。NSD2-IN-6可降低H3K36me2⽔平，并通过恢复雄激素受体(AR)信号通路来逆转细胞可塑性。NSD2-IN-6在类器官模型中能诱导细胞状态从簇2和簇3向簇1转变。NSD2-IN-6在体内通过逆转肿瘤细胞可塑性、抑制⽣长并促进细胞凋亡(apoptosis)来发挥抗肿瘤活性。NSD2-IN-6可⽤于前列腺癌的研究[1]。IC50&TargetEZH1EZH13.8nM(IC50)274nM(IC50)体外研究NSD2-IN-6(compoundNSD2i)showsasubstantialreductioninH3K36me2domainsinNPPO-1NEorganoids[1].NSD2-IN-6resultsasubstantialshiftfromclusterꢀ2and3statestowardstheclusterꢀ1stateandenrichmentofcanonicalARtargetexpressioninNPPO-1NEorganoids[1].NSD2-IN-6haslittleornoeffectonARexpressioninnon-neuroendocrineorganoidswithcombinedEnzalutamide[1].NSD2-IN-6(1ꢀµM,17days)increasessensitivitytoenzalutamideinNPPO-1NE,NPPO-2,NPPO-4andNPPO-6organoidswithEC50valuesof0.34,2.7,1.6and20µMrespectively[1].NSD2-IN-6(0.3-10µM,26days)notaffectonNSD2knockoutNPPO-1andNPPO-2organoids,hasaslighteffectonNSD2knockoutMSKPCa10[1].NSD2-IN-6(10µM,21days)reducesH3K36me2expressionandmodestupregulatesH3K27me3inMSKPCa10,MSKPCa14,WCM154,WCM1262andMSKPCa2humanCRPCorganoidlines,lossthelineagemarkerCD56andupregulatesARinWCM1262humanCRPCorganoidlines,resultsareductioninorganoidsizeandimmunostainingforcleavedcaspaseꢀ3inMSKPCa2organoids[1].NSD2-IN-6(0.3-10µM,21days)leadadecreasingcellviabilityafterenzalutamidetreatment,ahighBliss1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEsynergyscoreandaconcentration-dependentinductionofapoptosisinMSKPCa10,MSKPCa14,WCM154,WCM1262andMSKPCa2humanCRPCorganoidlineswhencombinatewithEnzalutamide[1].CellViabilityAssay[1]CellLine:H3K27me3inMSKPCa10,MSKPCa14,WCM154,WCM1262andMSKPCa2humanCRPCorganoidlinesConcentration:0.3,1,3and10μMIncubationTime:21daysResult:Progressivelydecreasedcellviabilityafterenzalutamidetreatment.ApoptosisAnalysis[1]CellLine:H3K27me3inMSKPCa10,MSKPCa14,WCM154,WCM1262andMSKPCa2humanCRPCorganoidlinesConcentration:0.3,1,3and10μMIncubationTime:21daysResult:Significantlyincreasedcaspase3andcaspase7activityinaconcentration-dependentmanner.体内研究NSD2-IN-6(compoundNSD2i)(75-300mg/kg,p.o.,oncedailyfor5days)reducesH3K36me2levelsinmicexenograftsofhumanprostateorganoids[1].NSD2-IN-6(150mg/kg,p.o.,dailyfor42days)exertsantitumoractivitybybyreversingplasticity,suppressinggrowthandpromotingtumourcellapoptosisinmicexenograftsofhumanprostateorganoids[1].AnimalModel:SubcutaneousgraftsofhumanCRPCorganoidsinNOD/SCIDmice[1]Dosage:75,150and300mg/kgAdministration:p.o.,dailyfor5daysResult:ReducedH3K36me2levelsateachconcentrationwithoutanyadverseeffectsonmousebodyweights.AnimalModel:SubcutaneousgraftsofhumanCRPCorganoidsinNOD/SCIDmice[1]Dosage:150mg/kgAdministration:p.o.,dailyfor42daysResult:HadmodesteffectsontumourgrowthforMSKPCa10,MSKPCa14andWCM1262xenografts.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResultedstronggrowthsuppressionwhencombinedwithEnzalutamide.DisplayedastrongresponseswhencombinedwithorwithnotEnzalutamide.Showedlossofneuroendocrinephenotypesaccompaniedbyovertnecrosisandfibrosis,andincreasedadenocarcinomafeaturesinMSKPCa10,MSKPCa14andWCM1262xenograftswhencombinewithEnzalutamide.ShowedLossofH3K36me2,neuroendocrinemarkersCHGAandSYPinMSKPCa10andMSKPCa14,andlossofCD56inWCM1262whencombinedwithEnzalutamide.DisplayedstrongdownregulationofKi67andupregulationofCC3whencombinewithEnzalutamide.REFERENCES[1].LiJJ,etal,.NSD2targetingreversesplasticityanddrugresistanceinprostatecancer.Nature.2026Jan;649(8095):216-226.McePd