Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEPROTACSTINGdegrader-4Cat.No.:HY-176180分子式: C??H??Cl?N?O?分子量: 837.7作用靶點(diǎn): PROTACs;STING;NF-κB;IKK作用通路: PROTAC;Immunology/Inflammation;NF-κB儲(chǔ)存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性PROTACSTINGdegrader-4是一種不含硝基的共價(jià)STINGPROTAC降解劑，DC50為3.23μM。PROTACSTINGdegrader-4可有效抑制STING及其下游信號(hào)傳導(dǎo)，例如p-TBK1和p-NF-κB(p-P65)以及免疫炎癥細(xì)胞因子。PROTACSTINGdegrader-4可減輕Cisplatin(HY-17394)誘發(fā)的急性腎損傷(AKI)小鼠模型中的腎臟和血液炎癥[1]。粉色：STINGligand(HY-176183)；藍(lán)色：CRBNligaseligand(HY-103596)；黑色：linker(HY-176182)；CRBNligaseligand+linker：HY-176181IC50&TargetNF-κBTBK1體外研究PROTACSTINGdegrader-4(Compound2h)(0.6-40μM,2-72h)dose-andtime-dependentlydegradesSTINGfor72h,withaDC50of3.23μM(24h)inTHP-1dualcells[1].PROTACSTINGdegrader-4(10μM,48h)inducesthedegradationofSTINGviatheproteasomepathway[1].PROTACSTINGdegrader-4(0.3-20μM,16h)dose-dependentlyreducedproteinlevelsofp-TBK1andp-NF-κB(p-P65),suppressingtheSTINGdownstreamsignalingcascadebeyonddirectdegradationofSTINGinTHP1-Dualcells[1].PROTACSTINGdegrader-4(0.6-20μM,2h)significantlyanddose-dependentlydecreasestheproductionofIFN-βandCXCL10andinhibitsIFNB1,CXCL10andISG15mRNAexpressioninTHP1-DualcellsinducedbyMSA-2(HY-136927)[1].PROTACSTINGdegrader-4(0.03-30μM,24-48h)exhibitsanoorweakcytotoxicityinTHP1-DualandRAW-Luciacells(below20μM)andinhumanandmousenormalcells(below30μM)[1].WesternBlotAnalysis[1]CellLine:THP-1dualcells1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEConcentration:0.6,1.2,2.5,5,10,20,40μMIncubationTime:2,4,8,12,24,48,72hResult:Dose-dependentlydegradedSTINGwithaDC50of3.23μM(24h)inTHP-1dualcells.ContinuouslyreducedtheexpressionlevelofSTINGinTHP1-dualcellsfor72hinTHP-1dualcells.InducedpotentdegradationofSTING,andthisdegradationeffectwasnotinhibitedbylysosomeinhibitorBAF(BafilomycinA1)(HY-100558)butwasreversedbyproteasomeinhibitorMG132(HY-13259)InducedthedegradationofSTINGviatheproteasomepathwayratherthanitswarheadmoleculeorE3ligaseligand,BAF(alysosomeinhibitor)andMG132(aproteasomeinhibitor).WesternBlotAnalysis[1]CellLine:THP-1dualcellsConcentration:0.3,0.6,1.25,2.5,5,10,20μMIncubationTime:2hfollowingMSA-2(10μM)for16hResult:Dose-dependentlyreducedproteinlevelsofp-TBK1andp-NF-κB(p-p65),suppressingtheSTINGdownstreamsignalingcascadebeyonddirectdegradationofSTING.RealTimeqPCR[1]CellLine:THP-1dualcellsConcentration:0.6,1.25,2.5,5,10,20μMIncubationTime:2hfollowingMSA-2(10μM)for24hResult:Significantlyanddose-dependentlyinhibitedIFNB1,CXCL10andISG15mRNAexpressioninTHP1-Dualcells.CellViabilityAssay[1]CellLine:THP1-Dual,RAW-Luciacells,humannormalcelllines(HEK293TandWI38VA-13)andmousenormalcelllines(HT22andMEF).Concentration:0.03,0.07,0.15,0.31,0.62,1.25,2.5,5,10,20μM(THP1-DualandRAW-Luciacells),1.1,3.3,10,30μM(fourhumanandmousenormalcelllines)IncubationTime:24,48hResult:Didnotexhibitsignificantinhibitionofcellularviabilitybelow20μMinTHP1-DualandRAW-Luciacells.2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEExhibitednoorweakcytotoxicityagainstfourhumanandmousecelllinesatconcentrationsbelow30μM.體內(nèi)研究PROTACSTINGdegrader-4(Compound2h)(30mg/kg,i.p.,dailyfor3days)significantlyrelievesrenalinflammationbydegradingSTINGanddownstreamsignalingpathways,suchasp-IRF3inCisplatin-inducedAKImicemodel[1].AnimalModel:MaleC57BL/6mice(8weeksold)weregivenCisplatinadministration(15mg/kg)1hafterPROTACSTINGdegrader-4toinduceAKImicemodel[1].Dosage:30?mg/kgAdministration:i.p.,dailyfor3?daysandthencollectedbloodandkidneysamplesaftercisplatininduction1.Result:Potentlymitigatedischemicsymptomsofkidneys.SignificantlyreducedtheproteinlevelofSTINGandp-IRF3inkidneytissues.EffectivelyreducedthemRNAlevelsofTnfα,Isg15andCxcl10.EffectivelysuppressedtheproductionofCXCL10,IFN-β,IL-6inplasma.REFERENCES[1].AnY,etal.DiscoveryofindolederivativesasSTINGdegraders.EurJMedChem.2025May12;2