1-2-4-Trimethoxybenzene-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemE1,2,4-TrimethoxybenzeneCat.No.:HY-W017087CASNo.:135-77-3分⼦式:C₉H₁₂O₃分⼦量:168.19作⽤靶点:NOD-likeReceptor(NLR);Caspase;InterleukinRelated作⽤通路:Immunology/Inflammation;Apoptosis储存⽅式:Storeatroomtemperature3years*Insolvent:-80°C,6months;-20°C,1month(Storeatroom

temperature3years)BIOLOGICALACTIVITY⽣物活性1,2,4-Trimethoxybenzene⼀种⼝服有效的NLRP3选择性抑制剂。1,2,4-Trimethoxybenzene可显著抑制Nigericin(HY-127019)或ATP(HY-B2176)诱导的NLRP3炎症⼩体活化，从⽽降低caspase-1活化和IL-1β分泌。1,2,4-Trimethoxybenzene特异性抑制NLRP3炎症⼩体的活化，⽽不响⿊⾊素瘤缺失2(AIM2)炎症⼩体的活化。1,2,4-Trimethoxybenzene抑制凋亡相关斑点样蛋⽩(ASC)的寡聚化以及NLRP3与ASC之间的蛋⽩-蛋⽩相互作⽤，从⽽阻断NLRP3炎症⼩体的组装。1,2,4-Trimethoxybenzene可⽤于研究实验性⾃⾝免疫性脑脊髓炎(EAE)，多发性硬化症和2型糖尿病[1][2][3]。IC50&TargetNLRP3Caspase-1IL-1β体外研究1,2,4-Trimethoxybenzene(0.5-1mM,1.5h)significantlyinhibitsNigericin(HY-127019)andLipopolysaccharides(HY-D1056)(LPS)-inducedNLRP3inflammasomeactivationinimmortalizedmurinebonemarrow-derivedmacrophages(iBMDMs),manifestedasreducedcaspase-1(Casp-1)cleavageandIL-1βsecretion[1].1,2,4-Trimethoxybenzene(1mM,75-90min)inhibitsLPSandATP-inducedNLRP3activationiniBMDMs,primarymicroglia,andPrimarymacrophagescells[1].1,2,4-Trimethoxybenzene(75-90min)inhibitsnigericin-inducedNLRP3activationiniBMDMsandprimarymacrophages,while1,2,3-TTBhadnoinhibitoryeffect,indicatingthattheinhibitoryactivityisstructure-dependent[1].1,2,4-Trimethoxybenzene(45min-2h)doesnotinhibitLPSandpoly(dA:dT)-inducedactivationofAIM2inflammasomeinprimaryperitonealmacrophagesandiBMDMs[1].1,2,4-Trimethoxybenzene(1h)reducestheformationofASCspecksiniBMDMsandPrimarymicrogliainducedbyLPSandnigericin:immunofluorescenceshowedasignificantreductioninthenumberofASC1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEspecks;DSScrosslinkingexperimentsshowedanincreaseinsolubleASCsandadecreaseininsolubleASCs[1].1,2,4-Trimethoxybenzene(1h)blockstheprotein-proteininteractionbetweenNLRP3andASCinLPS-inducediBMDMs[1].1,2,4-Trimethoxybenzene(1h)inhibitsLPSandnigericin-inducedNLRP3oligomerizationofiBMDMsandprimarymacrophages:DSScrosslinkingexperimentsshowedreducedformationofNLRP3monomers,dimersandhigheroligomers[1].WesternBlotAnalysis[1]CellLine:Immortalizedmurinebonemarrow-derivedmacrophages(iBMDMs)Concentration:0.5mM,1mMIncubationTime:1.5hResult:Caspase-1(Casp-1)cleavageandIL-1βsecretionarereduced.体内研究1,2,4-Trimethoxybenzene(200mg/kg,p.o.,oncedailyfor17days)significantlyalleviatesclinicalsymptoms,weightloss,anddemyelinatingpathologyinEAEmodelmice[1].1,2,4-Trimethoxybenzene(50-100mg/kg,p.o.,oncedailyfor3days)enhancestheextinctionoffearmemoriesandalleviatesPTSD-relatedanxietyanddepression-likebehaviorsinmicebyinhibitingtheNLRP3inflammasome[2].1,2,4-Trimethoxybenzene(50-200mg/kg,p.o.,oncedailyfor8weeks)improvesT2DM-relatedcognitivedysfunctionbyinhibitingNLRP3inflammasomeactivationandregulatinggutmicrobiotaintype2diabeticrats[3].AnimalModel:FemaleC57BL/6mice(6-8weeksold)weresubcutaneouslyinjectedwith150μgofMOG35-55peptide,andintraperitoneallyinjectedwith200ngofpertussistoxinonthedayofimmunization(day0)andday2,tosimulateEAE[1].Dosage:200mg/kgAdministration:P.o.,oncedailyfor17daysResult:Theincidenceofend-stagerenaldisease(ESRD)decreased,andclinicalsymptomsweresignificantlyalleviated.Significantlyreducedweightlossindicatesareductioninsystemicinflammatoryresponse.Theareaofmyelinbasicprotein(MBP)positiveinspinalcordsectionswassignificantlylargerthaninthecontrolgroup,indicatingareduceddegreeofdemyelination.Thepercentageofdemyelinatedareawassignificantlylowerthaninthecontrolgroup,confirmingtheprotectionofmyelinstructure.ASCspecksweresignificantlyreducedinspinalcordsections,suggestingthatNLRP3inflammasomeactivationwasinhibited.2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemETheexpressionofNLRP3,ASC,andcleavedcaspase-1proteinswasdownregulatedinspinalcordtissue.ThemRNAexpressionofpro-inflammatorycytokinesIFN-γandIL-17aandthechemokineCCL-5wasdecreasedinthespinalcord,whiletheexpressionoftheanti-inflammatorycytokineIL-4wasupregulated.AnimalModel:MaleC57BL/6mice(8weeksold)wereintraperitoneallyinjectedwithlipopolysaccharide(LPS,2mg/kg/d)for3consecutivedaystoinducedepressive-likebehavior[2].Dosage:50mg/kg,100mg/kgAdministration:P.o.,oncedailyfor3daysResult:Sucrosepreferencewassignificantlyincreased(withimproveddepressive-likebehavior),andimmobilitytimeinthetailsuspensiontest(TST)andforcedswimmingtest(FST)wassignificantlyreduced.ActivationofthehippocampalNLRP3inflammasomewasinhibited(e.g.,reducedexpressionofcleavedIL-1β,cleavedcaspase-1,andASCspotformation).AnimalModel:MaleSprague-Dawleyrats(8weeksold,200g)werefirstgivenahigh-sugar,high-fatdietfor5weeks,andthentype2diabetes(T2DM)wasinducedbyintraperitonealinjectionofstreptozotocin(STZ,30mg/kg)[3].Dosage:50mg/kg,100mg/kg,200mg/kgAdministration:P.o.,oncedailyfor8weeksResult:Significantimprovementswereobservedinbloodglucoselevels(FBG,OGTT-AUC),insulinresistanceindex(HOMA-IR),andbloodlipids(TC,TG,LDL-C)inrats,alongwithadecreaseinoxidativestressmarkers(MDA).Shortenedescapelatencyandincreasedtargetquadranttimeindicateenhancedlearningandmemoryabilities.ImprovedneuronalstructurewasobservedinthehippocampalCA1region,withELISAdetectingelevatedBDNFlevelsanddecreasedAChElevelsinthehippocampus.InhibitionofthehippocampalNLRP3inflammasomepathway(e.g.,reducedexpressionofNLRP3,ASC,caspase-1,GSDMD,andIL-1β).REFERENCES[1].PanRY,etal.1,2,4-TrimethoxybenzeneselectivelyinhibitsNLRP3inflammasomeactivationandattenuatesexperimentalautoimmuneencephalomyelitis.ActaPharmacolSin.2021Nov;42(11):1769-1779.doi:10.1038/s41401-021-00613-8IF:8.4Q1.Epub2021Feb24.Erratumin:ActaPharmacolSin