Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemESTING-IN-16Cat.No.:HY-175210分子式:C??H??ClN?O?分子量:433.93作用靶點(diǎn):STING;InterleukinRelated;IFNAR;ReactiveOxygenSpecies(ROS);Apoptosis作用通路:Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB;Apoptosis儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性STING-IN-16是一種STING抑制劑，其對(duì)STING抑制的IC50值分別為44nM(人)和32nM(鼠).STING-IN-16有效抑制人源細(xì)胞和小鼠細(xì)胞中STING軸的激活。STING-IN-16能恢復(fù)腎臟線粒體功能，抑制活性氧(ROS)的生成，并減少細(xì)胞凋亡(apoptosis)。STING-IN-16顯示出顯著的體內(nèi)抗炎效果STING-IN-16可用于自身免疫和自身炎癥性疾病的研究[1]。體外研究STING-IN-16(Compound5c)(1μM,24h)inhibitstheactivationofSTINGwithIC50sof44nM(THP1-Blue-ISGcells)and32nM(RAW-Lucia-ISGcells)[1].STING-IN-16(0.3-3μM,3-6h)inhibitstheSTINGsignalingpathwayactivatedbySTINGactivatorsandmarkedlyincreasesSTINGthermalstabilityinTHP1cells,BMDMcells,MEFcellsandRAW264.7murinemacrophagecells[1].STING-IN-16(1μM,6h)inhibitstheactivationofthecGAS-STINGaxistriggeredbyCisplatin(HY-17394)-inducedDNAdamage,whichinturnreducesROSaccumulationandcellapoptosisinHK2cells[1].WesternBlotAnalysis[1]CellLine:THP1cells,BMDMcells,HK2cellsConcentration:0.3,1,3μMIncubationTime:6hResult:InhibitedMSA-2(HY-136927)-stimulatedphosphorylationofSTING,TBK1,andIRF3,showingbetteractivitythanH151(HY-112693)inTHP1cells.InhibitedVadimezan(DMXAA)(HY-10964)-stimulatedphosphorylationofSTING,TBK1,andIRF3,showingbetteractivitythanH151inBMDMcells.1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEInhibitedcisplatin-stimulatedphosphorylationofSTING,TBK1,IRF3,andP65,exhibitinghigherpotencythanH151inHK2cells.Decreasedtheexpressionofapoptosismarkerssuchascleaved-caspase3,cleaved-caspase8,andDNAdamagemarkers(γ-H2A.Xandp-CHK1).RealTimeqPCR[1]CellLine:THP1cells,BMDMcells,HK2cellsConcentration:0.3,1,3μMIncubationTime:3,6hResult:InhibitedMSA-2-triggeredgeneexpressionofthecytokines(ISG15,ISG56,IFNβ,CXCL10andCCL5)dose-dependentlyinTHP1cells.InhibitedDMXAA-triggeredgeneexpressionofthecytokines(ISG15,ISG56,IFNβ,CXCL10andCCL5)dose-dependentlyinBMDMcells.InhibiteddiABZISTINGagonist-1(HY-112921A),cGAMP(HY-12512)andHTDNA-triggeredgeneexpressionofthecytokines(IFNβ,IL6,CXCL10andISG15)inTHP1cellsandBMDMcells.Reducedcisplatin-inducedgeneexpressionofinflammatorycytokinessuchasIL6,TNFA,IL8andCXCL10inHK2cells.ELISAAssay[1]CellLine:THP1cells,BMDMcellsConcentration:0.3,1,3μMIncubationTime:6hResult:DecreasedMSA-2-inducedsecretionofIFN-β,CXCL10,andIL-6,showingconsiderablyhigherpotencythanH151inTHP1cells.DecreasedDMXAA-inducedsecretionofIFN-β,CXCL10,andIL-6,showingconsiderablyhigherpotencythanH151inBMDMcells.CellViabilityAssay[1]CellLine:HK2cellsConcentration:1μMIncubationTime:6hResult:AttenuatedCisplatin-inducedcelldeath.體內(nèi)研究STING-IN-16(Compound5c)(10mg/kg,i.p.,dailyfor3days)alleviatesCisplatin-inducedinflammationin2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEmice[1].STING-IN-16(10mg/kg,i.p.,singledose)demonstratesanti-inflammatoryefficacyinMSA-2-inducedinflammatorymousemodels[1].AnimalModel:Cisplatin-inducedkidneyinjuryC57BL/6malemice(8weeks)[1]Dosage:10mg/kgAdministration:i.p.dailyfor3daysResult:BlockedtheexpressionofIfnb,Il6,andTnfa.Reducedcisplatin-inducedBUNelevation.Alleviatedcisplatin-inducedpathologicalchanges(severetubulardilation,tubularnecrosis,andcastformation).Reducedcisplatin-inducedelevationofplasmaIL-6,whichwasbetterthanthatofH151.Restoredtheexpressionofsuchmitochondria-encodedgenes(mt-CO1,mt-CO2,mt-CO3,mt-ATP6,mt-ND2andmt-ND4).AnimalModel:MSA-2-inducedinflammationC57BL/6malemice(8weeks)[1]Dosage:10mg/kgAdministration:i.p.forasingledoseResult:DecreasedMSA-2-inducedcytokinessecretioninserum,includingIFN-β,CXCL10,andIL-6.DiminishedMSA-2-inducedexpressionofIfnbandIl6inthekidneytissue.LoweredMSA-2-stimulatedexpressionofIfnb,Il6,andCcl5inthehearttissue.REFERENCESZhouX,etal.Discoveryof3,4-dihydroisoquinoline-2(1H)-carboxamideSTINGinhibitorsasanti-inflammatoryagents.EurJMedChem.2025Jul1;2