MS1-96-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMS1-96Cat.No.:HY-179558分⼦式:C₂₅H₂₉NO₂分⼦量:375.5作⽤靶点:PD-1/PD-L1作⽤通路:Immunology/Inflammation储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性MS1-96⼀种具有⼝服活性的PD-L1(程序性死亡配体1)降解剂。MS1-96能有效降低多种结直肠癌(CRC)细胞系中PD-L1蛋⽩的表达⽔平。敲低HIP1R后，MS1-96丧失了诱导PD-L1降解的能⼒。MS1-96可直接与PD-L1结合(KD=2.58μM)，并增强HIP1R与PD-L1之间的相互作⽤，从⽽改变PD-L1在⽹格蛋⽩包被囊泡内的细胞内转运。MS1-96可诱导PD-L1的异常N-糖化，导致蛋⽩不稳定并加速其溶酶体介导的降解。MS1-96可⽤于结直肠癌的研究[1]。IC50&TargetPD-L12.58μM(Kd)体外研究MS1-96(10μM,48h)significantlyreducesPD-L1proteinlevelsinRKOcellsbutshowsnoreductioninPD-L1mRNAlevelsinRKOcells[1].MS1-96(0-3μM,0-48h)inducesPD-L1degradationinRKOcellsinatime-anddose-dependentmanner[1].MS1-96(1.5μM,24h)reducesthelevelofPD-L1onthesurfaceofRKOandLoVocells[1].MS1-96(1.5μM,24h)disruptsthePD-1/PD-L1interactionbydownregulatingPD-L1inRKOandLoVocells[1].MS1-96(1.5μM,24h)enhancesthekillingeffectofTcellsonRKOcellsandreducedthenumberofsurvivingcells[1].MS1-96(1.5μM,24h)increasesLDHreleaseinRKOcellsfollowingco-culturewithactivatedPBMCs,indicatingenhancedcytotoxicity[1].MS1-96(1.5μM,0-12h)promotesthedegradationofPD-L1inexistingRKOcells,ratherthaninhibitingtranslation,thusreducingPD-L1levels[1].MS1-96(1.5μM)degradesPD-L1inRKOcellsviathelysosomalpathway,independentofproteasomesorautophagy[1].1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMS1-96inducesaberrantN-glycosylationofPD-L1atN35,N192,N200,andN219sitesinRKOcells[1].体内研究MS1-96(0-400mg/kg,p.o.,oncedailyfor10days)effectivelyinhibitscolorectalcancertumorgrowthinMC38cellxenograftmicebydownregulatingPD-L1,withagoodsafetyprofile[1].MS1-96(0-400mg/kg,p.o.,oncedailyfor9days)failstoinhibitMC38tumorgrowthinimmunodeficientMC38cellxenograftmice[1].MS1-96(200mg/kg,p.o.,oncedailyfor8days)showsantitumoractivityinMC38cellxenograftmicethatwasstrictlydependentonCD8+Tcells[1].AnimalModel:C57BL/6mice(female,5weeksold)weresubcutaneouslyinoculatedwith8×105MC38colorectalcancercells[1].Dosage:0mg/kg,100mg/kg,200mg/kg,400mg/kgAdministration:P.o.,oncedailyfor10daysResult:ThedrugsignificantlyinhibitedthegrowthofMC38tumorsinadose-dependentmanner.Tumorvolumeandweightweresignificantlyreduced.Nosignificantchangeinmousebodyweightindicatedgooddrugtolerance.WesternblotanalysisshowedasignificantdecreaseinPD-L1proteinlevelsintumortissues.AnimalModel:Immunodeficientnudemice(female,4weeksold)weresubcutaneouslyinoculatedwith8×105MC38colorectalcancercells[1].Dosage:0mg/kg,200mg/kg,400mg/kgAdministration:P.o.,oncedailyfor9daysResult:FailedtoinhibitthegrowthofMC38tumors.AnimalModel:C57BL/6mice(female,5weeksold)weresubcutaneouslyinoculatedwith8×105MC38colorectalcancercells.Twodaysbeforetumorinoculation,anti-CD4andanti-CD8antibodieswereadministeredviaintraperitonealinjection[1].Dosage:200mg/kgAdministration:P.o.,oncedailyfor8daysResult:DepletionofCD8+TcellsaloneorsimultaneousdepletionofCD4+andCD8+Tcellshadnoanti-tumoreffect.DepletionofCD4+Tcellsalonedidnotaffecttheanti-tumoreffect.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].PengJJ,etal.MS1-96inducesHIP1R-dependentPD-L1degradationandpromotesantitumorimmunityincolorectalcancer.ActaPharmacolSin.2025Nov3.McePdfHeightCaution:Produ