Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemESF-9-2Cat.No.:HY-175236CASNo.:3053768-78-5分子式:C??H??F?N?O?分子量:515.55作用靶點(diǎn):PD-1/PD-L1;Apoptosis;ERK;JNK;Cadherin;p38MAPK;GSK-3;IFNAR;Caspase;Bcl-2Family作用通路:Immunology/Inflammation;Apoptosis;MAPK/ERKPathway;StemCell/Wnt;Cytoskeleton;PI3K/Akt/mTOR儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 SF-9-2是一種PD-L1/PD-1結(jié)合抑制劑(IC50=24.9nM)。SF-9-2抑制了SK-N-SH細(xì)胞的上皮間質(zhì)轉(zhuǎn)化、遷移、侵襲和增殖，還誘導(dǎo)其凋亡(apoptosis)和細(xì)胞周期停滯。SF-9-2通過MAPK信號(hào)通路阻斷PD-L1誘導(dǎo)的SK-N-SH細(xì)胞生長。SF-9-2恢復(fù)GSK-3β活性，并通過泛素-蛋白酶體通路增強(qiáng)PD-L1降解。SF-9-2抑制了SK-N-SHNOG小鼠模型中的腫瘤生長，且無明顯毒性。SF-9-2還可作為免疫檢查點(diǎn)抑制劑，阻斷PD-L1以恢復(fù)T細(xì)胞功能。SF-9-2可用于神經(jīng)母細(xì)胞瘤研究[1]。IC50&TargetGSK-3βGSK-3βCaspase3體外研究SF-9-2(0.5-16μM,48h)exhibitssignificantinhibitoryactivityagainstSK-N-SH(IC50=5.9μM)andSK-N-AScells(IC50=8.67μM)buthasminimalinhibitoryeffectsonSH-SY5YandSK-N-BE(2)cells,andexhibitsweakcytotoxiceffectsonnormalcellMRC-5(IC50=12.15μM)[1].SF-9-2(1-6μM,24h)inhibitstheproliferation,migration,invasionandepithelial-mesenchymaltransition(EMT),andinducesmitochondria-dependentapoptosisandcellcyclearrestinSK-N-SHcells[1].SF-9-2(2.5-8μM,24-48h)inhibitstheMAPKpathwayanddownregulatesPD-L1LevelsthroughtargetingtheERKsignalingpathwayinSK-N-SHCells[1].SF-9-2(2.5-5μM,24h)inducesPD-L1internalizationandproteasomaldegradationmediatedbyGSK-3βinSK-N-SHCells[1].SF-9-2(2.25-200nM)decreasesthefluorescencesignal,effectivelyblockingthePD-1/PD-L1immunecheckpointin293TcellsoverexpressingPD-1andFc-PD-L1protein[1].SF-9-2(1-16μM,48h)increasedthesecretionlevelofIFN-γinPBMCsandshowsnoobvioustoxicitytoPBMCsatconcentrationsof1,2,and4μM[1].1/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemESF-9-2(1-8μM,48h)canexhibitbothdirecttumoricidalactivityandTcell-mediatedcytotoxicityagainstSK-N-SHcells[1].CellMigrationAssay[1]CellLine:SK-N-SHcellsConcentration:1μM,2μM,4μMIncubationTime:24hResult:Inhibitedthemigration,reducedthenumberofcellspassingthroughthechamber,withthemigrationrateinthe1,2,4μMgroupwas73.3%,43.0%,13.4%,respectively.WesternBlotAnalysis[1]CellLine:SK-N-SHcellsConcentration:2.5μM,5μMIncubationTime:24h,48hResult:Up-regulatedtheexpressionsofN-cadherinandE-cadherin,anddown-regulatedtheexpressionsofβ-catenin,andvimentin.ReducedtheBcl-2/BAXratioandincreasedthecleavageofCaspase3.ReducedthephosphorylationlevelsofERKandJNK,andincreasedthephosphorylationlevelofp38at48h.ReducedPD-L1levelsat5μM.Reducedthelevelofp-GSK-3β(Ser9),weakenedtheinhibitoryeffectofp-ERKonGSK-3βtoacertainextent,andpromotedtheactivationofGSK-3βat5μM.ApoptosisAnalysis[1]CellLine:SK-N-SHcellsConcentration:1μM,3μM,6μMIncubationTime:24hResult:Inducedapoptosis,withtheproportionofearlyandlateapoptoticcellsincreasinginadose-dependentmanner.CellCycleAnalysis[1]CellLine:SK-N-SHcellsConcentration:1μM,3μM,6μMIncubationTime:24h2/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult:IncreasedtheproportionofcellsintheG1/SphasewhiledecreasingthepercentageofcellsintheG2phase.WesternBlotAnalysis[1]CellLine:PD-L1knockdownSK-N-SHcellsConcentration:2.5μM,5μMIncubationTime:24hResult:WasweakerthanthatinnormalSK-N-SHcellsforthedownregulationofERKphosphorylation.Immunofluorescence[1]CellLine:SK-N-SHcellsConcentration:2.5μMIncubationTime:24hResult:ReducedPD-L1onthecellsurface(redfluorescence)andinternalizeditintothecytoplasmascompoundconcentrationincreases.ELISAAssay[1]CellLine:PBMCsConcentration:1μM,2μM,4μMIncubationTime:48hResult:IncreasedthesecretionlevelofIFN-γat4μM.體內(nèi)研究SF-9-2(20-40mg/kg,i.p.,onceaday,21days)suppressesSK-N-SHtumorgrowthinNOGmicemodel[1].AnimalModel:SK-N-SHtumor(50millioncells/mL,s.c.)femaleNOGmice(5weeksold,17-20g)model[1]Dosage:20mg/kg,40mg/kgAdministration:i.p.,onceaday,21daysResult:Inhibitedtumorgrowth,withtumorinhibitionratesof23.79%(20mg/kg)and69.45%(40mg/kg)respectively.Hadnoeffectsonbodyweightormortality,exhibitednoapparentnephrotoxicityor3/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEhepatotoxicity.REFERENCESJianweiWangetal.AntineuroblastomaActivityEvaluationandMechanismofNovelPD-L1SmallMoleculeInhibitorsthroughImmuneandNon-ImmunePathways.ACS