Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESulindacsodiumCat.No.:HY-B0008ACASNo.:63804-15-9Synonyms:MK-231sodium分?式:C??H??FNaO?S分?量:378.39作?靶點:NF-κB;PD-1/PD-L1作?通路:NF-κB;Immunology/Inflammation儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Sulindac(MK-231)?種?服活性?甾體類抗炎藥。Sulindac也?種免疫調節(jié)劑。Sulindac可?于脊柱關節(jié)炎、痛風性關節(jié)炎及多種癌癥如結直腸癌、肺癌的研究。體外研究Sulindac(MK-231)(500μM,48h)sodiumiseffectiveinpreventingTGF-β1-inducedEMT,asindicatedbyupregulationoftheepithelialmarker,E-cadherin,anddownregulationofmesenchymalmarkersandtranscriptionfactors[1].Sulindacsodium(500μM,48h)caninhibitTGF-β1-enhancedmigrationandinvasionofA549cells[1].Sulindacsodium(500μM,48h)enhancesthereversalofTGF-β1-inducedEMTbysulindac(sodium)andSIRT1upregulationpromotedTGF-β1-inducedEMT[1].WesternBlotAnalysis[1]CellLine:A549cellsConcentration:500μMIncubationTime:48hResult:Inhibittransforminggrowthfactor(TGF)-β1-inducedepithelial-mesenchymaltransitioninA549cells.Immunofluorescence[1]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:A549cellsConcentration:500μMIncubationTime:48hResult:ReversedSIRT-1expressionbyTGF-β1andinhibitedtheTGF-β1-inducedcadherinswitch.CellMigrationAssay[1]CellLine:A549cellsConcentration:500μMIncubationTime:48hResult:Inhibitedmigration,decreasedresistanceco-treatmentwithTGF-β1.CellInvasionAssay[1]CellLine:A549cellsConcentration:500μMIncubationTime:40h;48hResult:CouldeffectivelyinhibittheTGF-β1-inducedincreaseininvasionbylungcancercells.體內研究Sulindac(MK-231)sodium(15mg/kg,p.o.,bid(sulindacalone);7.5mg/kgp.o.,bid(sulindaccombinationwithPD-L1))showsasignificantreductionintumorvolumeandincreasesinfiltrationofCD8+Tlymphocytesinthetumortissueswhentreatedwithcombinationtherapy[2].Sulindacsodium(15mg/kg,p.o.,bid(sulindacalone);7.5mg/kgp.o.,bid(sulindaccombinationwithPD-L1))candownregulatePD-L1byblockingNF-κBsignaling,whichinturnledtoadecreaseinexosomalP[2].Sulindacsodium(15mg/kg,p.o.,bid(sulindacalone);7.5mg/kgp.o.,bid(sulindaccombinationwithPD-L1))leadstoincreasedavailabilityofPD-L1AbbydownregulatingPD-L1incombinationtherapy[2].SulindacsodiumhasnotasystemicinhibitoryeffectonprostaglandinE2(PGE2)inlow-dosedoes[2].AnimalModel:CT26syngeneicmousetumormodel[2]Dosage:15mg/kg;7.5mg/kgAdministration:15mg/kg,p.o.,bid(sulindacalone);7.5mg/kgp.o.,bid(sulindaccombinationwithPD-L1)Result:DownregulatedPD-L1throughtheblockadeofNF-κBsignalingandmodulatetheresponseofpMMRCRCtoanti-PD-L1immunotherapy.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:CT26syngeneicmousetumormodel[2]Dosage:15mg/kg;7.5mg/kgAdministration:15mg/kg,p.o.,bid(sulindacalone);7.5mg/kgp.o.,bid(sulindaccombinationwithPD-L1)Result:DownregulatedPD-L1throughtheblockadeofNF-κBsignalingandmodulatetheresponseofpMMRCRCtoanti-PD-L1immunotherapy.CoundeffectivelyinhibitPD-L1withnosignificantsystematictoxicity.REFERENCES[1].Byong-KiCha,etal.CelecoxibandsulindacinhibitTGF-β1-inducedepithelial-mesenchymaltransitionandsuppresslungcancermigrationandinvasionviadownregulationofsirtuin1.Oncotarget.2016Aug30;7(35):57213-57227.[2].BinYi,etal.SulindacModulatestheResponseofProficientMMRColorectalCancertoAnti-PD-L1Immunotherapy.MolCancerTher.2021Jul;20(7):1295-1304.McePdfHeightCaution:Produc