SMU-C409-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESMU-C409Cat.No.:HY-180580分⼦式:C₂₁H₂₁N₃OS₂分⼦量:395.54作⽤靶点:Toll-likeReceptor(TLR);MyD88;NF-κB;TNFReceptor;InterleukinRelated作⽤通路:Immunology/Inflammation;NF-κB;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性SMU-C409⼀种TLR1/2激动剂，在HEK-BluehTLR2细胞中的EC50值为65nM。SMU-C409可激活TLR1/2–MyD88–NF-κB通路，诱导TNF-α/IL-1β分泌，并强烈激活免疫细胞，从⽽发挥抗肿瘤免疫调节作⽤。SMU-C409在体外表现出较低的毒性，可⽤于癌症免疫的研究[1]。体外研究SMU-C409(0-100nM)selectivelyactivatesthehTLR2signalingpathwayinHEK-BluehTLR2cellswhileshowingnegligibleactivityonotherTLRsubtypes(hTLR3/4/7/8)[1].SMU-C409(0-100μM,24h)showslowtoxicityinHEK-BluehTLR2cells,PBMC,B16−F10cellsandMCF-7cells[1].SMU-C409(0-50μM,0-24h)specificallytargetsandactivatesTLR2inHEK-BluehTLR2andTHP-1cells[1].SMU-C409(0-100μM,0-700min)bindshTLR2proteinwiththeKdof72.4nM[1].SMU-C409(0-20μM,0-120min)activatestheTLR1/2heterodimer,triggeringdownstreamsignalingviaMyD88recruitment,whichpromotesphosphorylationofMyD88-NF-κBpathwaycomponentsanddissociationofinhibitoryproteinsinTHP-1(Phorbol12-myristate13-acetate(HY-18739)PMAdifferentiated)cells[1].SMU-C409(0.01-10μM,24h)playsapivotalroleininflammatorysignalingbystimulatingdownstreamcytokineproductionthroughtheNF-κBpathwayandmaintainsconservedspeciesspecificityacrossdifferentimmunecelltypesandsignalingaxesinTHP-1cells(PMA-differentiated),PBMCcells,mouseperitonealmacrophagesandmouseRAW264.7cells[1].SMU-C409(0-10μM,48h)exhibitsadegreeofimmuneactivatingactivityinCD3+cells,CD4+cells,CD8+cells,Monocytes,BcellsandNKcells[1].SMU-C409(1-20μM,24h)enhancesimmunecellmediatedinductionofSJSA-1apoptosis,showingthepotentialforantitumorimmuneactivity[1].1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESMU-C409(8h)exhibitsmarkedlyimprovedplasmastabilitywithdegradationrateconstant(k)of0.0003min-1inratplasma[1].CellCytotoxicityAssay[1]CellLine:HEK-BluehTLR2cells,PBMC,B16−F10cellsandMCF-7cellsConcentration:0,0.14,0.41,1.23,3.7,11.11,33.3and100μMIncubationTime:24hResult:ShowednoobvioustoxicitytoHEK-BluehTLR2cells,peripheralbloodmononuclearcells(PBMC),B16−F10cellsorMCF-7cellsatahighconcentrationof100μM.WesternBlotAnalysis[1]CellLine:HEK-BlueTLR2cellsorTHP-1cellsConcentration:0,0.01,0.1,1,10,or50μMIncubationTime:0,15,30,60,90,or120minResult:ShowedSMU-C409dosedependentlyupregulatedTLR2expressioninbothHEK-BluehTLR2cellsandPMA-differentiatedTHP-1cells.ELISAAssay[1]CellLine:Wild-typeTHP-1cellsandTLR2knockdownTHP-1cellsConcentration:20,40μMIncubationTime:24hResult:InducedTNF-αinwild-typecellsbutnotinTLR2-knockdowncells.WesternBlotAnalysis[1]CellLine:THP-1(PMAdifferentiated)cellsConcentration:0,10and20μMIncubationTime:0,15,30,60,90,120minand24hResult:UpregulatedTLR1andTLR2proteinexpressionafter24hstimulationat20μM.Inducedtime-dependentphosphorylationofIKKα/β,p65,andp38(evidentby15min,withpeakdynamicsvaryingbyprotein)andprogressiveIκBαdissociationinTHP-1cells,coupledwithsubsequentIκBαrecoveryby120min.ELISAAssay[1]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:THP-1cells(PMA-differentiated),PBMCcells,mouseperitonealmacrophagesandmouseRAW264.7cells.Concentration:0,0.01,0.1,1,5and10μMIncubationTime:24hResult:InduceddosedependentsecretionofTNF-αandIL-1βinbothfreshlyisolatedhumanPBMCsandPMA-differentiatedTHP-1cells.ShowednosignificanteffectonTNF-αandIL-6secretioninmurineperitonealmacrophages.Failedtoelicitconcentration-dependentNOactivationinmouseRAW264.7cells.ApoptosisAnalysis[1]CellLine:SJSA-1(GFPlabeled),JurkatTcells,andPMA-differentiatedTHP-1cellsConcentration:0,0.01,0.1,1,5and10μMIncubationTime:24hResult:Resultedthespontaneousapoptosisrate(4.91%)ofSJSA-1cells.Resultedanincreaseapoptosisratefrom7.69to13.77%.inSJSA-1cellscoculturedwithJurkatTandPMA-differentiatedTHP-1cells.REFERENCES[1].ChenZ,etal.Synthesis,andStructure-ActivityRelationshipofN-Aryl-N'-(thiophen-2-yl)thioureaDerivativesasNovelandSpecificHumanTLR1/2AgonistsforPotentialCancerImmunotherapy.JMedChem.2021Jun1