MyD88-IN-3-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMyD88-IN-3Cat.No.:HY-178136分⼦式:C₂₄H₂₄N₆O₅S分⼦量:508.55作⽤靶点:Toll-likeReceptor(TLR);MyD88;p38MAPK;NF-κB;JNK作⽤通路:Immunology/Inflammation;MAPK/ERKPathway;NF-κB储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性MyD88-IN-3⼀种具有⼝服活性的选择性MyD88抑制剂。MyD88-IN-3特异性靶向MyD88的TIR结构域(KD=28.5μM)，从⽽阻⽌MyD88⾃聚合及其与TLR的相互作⽤，从⽽抑制MAPK和NF-κB通路的激活。MyD88-IN-3表现出显著的抗炎效果，并有效缓解CLP(盲肠结扎和穿刺)和脂多糖(HY-D1056)(LPS)诱导的ALI模型中的急性肺损伤症状。MyD88-IN-3可⽤于ALI的研究[1]。体外研究MyD88-IN-3(Compound3g)(1.1-30μM)demonstratespotentanti-inflammatoryeffectsbysignificantlyinhibitingIL-6secretioninthemousemacrophageJ774A.1(IC50=1.32μM)andhumanTHP-1(IC50=0.75μM)macrophagesdifferentiatedwithPMA[1].MyD88-IN-3(10μM,pretreatmentfor2h,followedbyco-treatmentwith0.5μg/mLLPSfor30minutes)restoresthedecreasedexpressionlevelofIκBαinducedbyLPS,significantlyreducesthephosphorylationofp38,inhibitsthephosphorylationofJNK,suppressesphosphorylationandnucleartranslocationofp65,andinhibitsLPS-inducedactivationoftheMAPKpathway,leadingtonucleartranslocationofc-JuninJ774A.1macrophage[1].MyD88-IN-3(5μM,10μM)caninhibitMyD88homodimerizationinJ774A.1[1].MyD88-IN-3(10μM,2h)caninhibittheinteractionbetweenMyD88andTLR4inJ774A.1[1].MyD88-IN-3(10μM,4h)improvesthethermalstabilityofMyD88,preservingroughly50%ofMyD88at64°C[1].MyD88-IN-3bindsefficientlytotheTIRdomain(KD=28.5μM),whileexhibitingnobindingaffinityfortheDDdomain(KD=1.32M)[1].WesternBlotAnalysis[1]CellLine:J774A.1mousemacrophages1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:Pretreatmentfor2h,followedbyco-treatmentwith0.5μg/mLLPSfor30minutes.IncubationTime:2hResult:RestoredLPS-inducedIκBαdegradationandinhibitedp38andJNKphosphorylation.体内研究MyD88-IN-3(500mg/kg,1000mg/kg,oralgavage,oncedailyfor10days)exhibitsadvantageousinvivosafetyinSDrats[1].MyD88-IN-3(20mg/kg,Oralgavage,pretreated6h)mitigatessepsis-inducedALIinC57BL/6mice[1].MyD88-IN-3(20mg/kg,Oralgavage,pretreated30min)AttenuatedLPS-InducedALIinC57BL/6mice[1].AnimalModel:SDrats[1]Dosage:500mg/kg,1000mg/kgAdministration:Oralgavage,oncedailyfor10daysResult:Inducedaslightdecreaseinbodyweightinthefirstday,followingwhichbodyweightprogressivelyreturnedtolevelsakintothecontrolgroup,withnostatisticallysignificantdifferencesnoted.Indicatednonotablepathologicalalterationsintheorgansofmice.AnimalModel:MaleC57BL/6mice,weighingbetween18and22g,aftertheadministrationofanesthesia,anabdominalincisionwasperformedtorevealthececum.Thececumwasligatedbeneaththeileocecalvalvewithsurgicalthreadandsubsequentlypuncturedoncewithaneedle.Theabdominalincisionwassubsequentlysuturedclosedafterrepositioning[1]Dosage:20mg/kgAdministration:Oralgavage,administer6hoursbeforeCLPsurgeryResult:Markedlydiminishedthelungwet/dryweightratio,demonstratingitseffectivenessinalleviatingsepsis-inducedlungedema.ObstructedthiscellularinfluxintoBALF,suggestingthatMyD88-IN-3alleviatessepsis-inducedpulmonaryedema.ledtoasignificantdecreaseinIL-6.Alleviatedlungtissuedamage,interstitialedema,pulmonarycongestion,inflammatoryinfiltration,andthickenedalveolarsepta.Significantlydiminishedimmunecellinfiltration,therebymitigatingtheinflammatoryresponse.AnimalModel:LPS-InducedMaleC57BL/6mice,weighingbetween18and22g2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDosage:20mg/kgAdministration:Oralgavage,administer30minbeforeLPS.Result:Markedlydiminishedthelungwet/dryweightratio,demonstratingitseffectivenessinalleviatingsepsis-inducedlungedema.SignificantlysuppressedtheincreaseintotalproteinconcentrationandthedischargeofimmunecellsintoBALF.Decreasedspleenweightandmitigatedinflammation.MarkedlyreducedIL-6levelsinbothbronchoalveolarlavagefluidandserumsamples.Mitigatedaugmentedalveolarseptalthickness,pulmonarycongestion,inflammatoryinfiltration,andlungtissuedegradation.Reducedleukocyteinfiltrationintothealveoli.REFERENCES[1].ChenP,etal.DiscoveryofMyD88-IN-3asanOrallyBioavailable,TIRDomainSelective,andPotentMyD88InhibitorfortheTreatmentofAcuteLungInjury.JMedChem.2025Sep2