MW073-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMW073Cat.No.:HY-178323CASNo.:3048608-87-0分?式:C??H??N?分?量:361.48作?靶點:5-HTReceptor;Arrestin作?通路:GPCR/GProtein;NeuronalSignaling儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性MW073?種?選擇性、?服有效的5-HT2BR拮抗劑(IC50=70nM)。MW073通過濃度依賴性地抑制受體活性和β-arrestin-1募集發(fā)揮作?。MW073可改阿爾茨海默病(AD)??模型的突觸可塑性和?為缺陷，包括攻擊?為。MW073可?于阿爾茨海默病相關(guān)研究[1][2]。IC50&Target5-HT2BReceptor70nM(IC50)體外研究MW073(0.1-10μM)demonstratesthatitsbiochemicalmechanismofactionforbothh5-HT2BR(Kd=86nM,EC50Gprotein=1.1μM,EC50β-Arrestin1=2.4μM)andm5-HT2BR(Kd=125nM,EC50Gprotein=6.7μM,EC50β-Arrestin1=0.6μM)isthedose-dependentinhibitionofbothserotonin-inducedactivation/β-arrestin-1recruitmentandbasalconstitutiveactivityintransfectedHEK293Acells,suggestinginverseagonism[1].MW073exhibitsonly5-HT2BRantagonistactivitywhensubjectedtolarge-scalecellularscreeningof165diverseGProtein-CoupledReceptors(GPCRs)foragonistandantagonistactivityusingapanelofstablytransfectedCHOcelllines[1].MW073exhibitsnoactivityagainstkinases,keyenzymes,ortransporters,anditslackofCYP450substratestatuspredictslowdrug-interactionpotential[1].體內(nèi)研究MW073(5mg/kg,i.p.,30minpriortotest)rapidlyrescuesacutedeficitsinsynapticplasticityandmemoryinducedbyamyloidbeta(Aβ)ortauoligomersinC57BL/6Jmice[1].MW073(0-5mg/kg,p.o.,q.d.for30-45daysstartingattheageofday60-70)dose-dependentlypreventsandamelioratesmemorydeficitsinAPP/PS1mice[1].MW073(5mg/kg,p.o.,q.d.for~150-250days)restoressynapticandmemoryfunctioninhTau/Mapt-KOmice,provingeffectiveinbothpreventiveandtherapeuticinterventionparadigmsduringchronictreatment1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].MW073(5mg/kg,i.p.,q.d.for3weeks)reducesaggressivebehaviorwithoutinducingsedationorhypoactivityinTg2576mice[2].AnimalModel:C57BL/6Jmice(3-4monthsold)infusedwith200nMAβ-or500nMtau-oligomersorvehicle(intrahippocampal,20minpriortotest)[1]Dosage:5mg/kgAdministration:i.p.,30minpriortotestResult:AttenuatesbothAβ-andtau-oligomer-inducedsynapticdysfunction.Rescuedlong-termpotentiation(LTP)deficitinhippocampalslicestreatedwithAβortauoligomers(perfusedat1.9μM).Reducederrorsinthe2-dayradialarmwatermaze(RAWM)inducedbyAβortauoligomers.AttenuatedbothAβ-andtau-oligomer–inducedreductioninfreezinginthecontextualfearconditioning(FC).AnimalModel:hTau/Mapt-KOmice(7monthsold)[1]Dosage:5mg/kgAdministration:p.o.,q.d.for~250days(priortosignificantpathology)Result:PreventedtheimpairmentofLTP.Re-establishedthenormalnumberoferrorsintheRAWM(~180days).ProtectedagainsttheimpairmentofassociativememoryincontextualFC(~240days).AnimalModel:APP/PS1transgenicmice(3-4monthsold)[1]Dosage:0-5mg/kgAdministration:p.o.,q.d.for30-45daysstartingattheageofday60-70Result:Dose-dependentlyreducedthenumberoferrorsintheradialarmwatermaze(RAWM).AmelioratedthecontextualFCdefectinadose-dependentmanner.ED50forRAWMimprovementwas1.886mg/kg.AnimalModel:hTau/Mapt-KOmice(11monthsold)[1]Dosage:0-5mg/kgAdministration:p.o,q.d.for~150days(afterpathologyonset)Result:RestoredthecapabilityofundergoingLTP.ProtectedagainsttheimpairmentofspatialmemoryintheRAWM(~45days).2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEProtectedagainsttheimpairmentofassociativememoryincontextualFC(~140days).AnimalModel:MaleTg2576mice[2]Dosage:5mg/kgAdministration:i.p.,q.d.for3weeksResult:Significantlyreducedaggressivebehaviorcomparedtothevehiclecontrolgroupintheresident-intrudertest.Decreasedthedurationofthefirstattack.Decreasedthenumberofattacksandthetotalattacktime.Revealednosignificantdifferencesinthetimespentinthecenterversustheperipheryofthearena,numberofentriesintothecenter,andtotaldistancetraveled.Didnotalterlocomotorfunction,anxiety-likebehavior,orexploratoryactivity.REFERENCES[1].RoySM,etal.Optimized5-HT2binhibitorsforneuropsychiatricsyndromeswithcognitivedysfunction.AlzheimersDement(NY).2025Mar27;11(1):e70073.[2].AcquaroneE,etal.TheHighlySelective5-HT2BReceptorAntagonistMW073MitigatesAggressiveBehaviorinanAlzheimer’sDiseaseMouseM