2-PMPA-2-Phosphonomethyl-pentanedioic-acid-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemE2-PMPACat.No.:HY-100788CASNo.:173039-10-6Synonyms:2-(Phosphonomethyl)pentanedioicacid分?式:C?H??O?P分?量:226.12作?靶點(diǎn):Carboxypeptidase作?通路:MetabolicEnzyme/Protease儲存?式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn)H2O:≥28mg/mL(123.83mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM4.4224mL22.1122mL44.2243mL5mM0.8845mL4.4224mL8.8449mL10mM0.4422mL2.2112mL4.4224mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(storedundernitrogen)。-80°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：PBS1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:100mg/mL(442.24mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性2-PMPA?效選擇性的?氨酸羧肽酶II(GCPII)抑制劑，IC50值為300pM。IC50&TargetIC50:300pM(GCPII)[1]體外研究2-PMPAisapotentandselectiveinhibitorofGCPII,anenzymewhichcatabolizestheabundantneuropeptideN-acetyl-aspartyl-glutamate(NAAG)toN-acetylaspartate(NAA)andglutamate.2-PMPAdemonstratesrobustefficacyinnumerousanimalmodelsofneurologicaldisease.2-PMPAisahighlypolarcompoundwithmultiplenegativechargescausingsignificantchallengesforanalysisinbiologicalmatrices[1].2-PMPAreducesketamine-induceddecreaseofcellviabilityandincreaseofLDHlevelsinthemixedculturesbutnotintheneuronalcultures[2].體內(nèi)研究Intraperitonealadministrationof100mg/kg2-PMPAresultsinmaximumconcentrationinplasmaof275μg/mLat0.25h.Thehalf-life,areaunderthecurve,apparentclearance,andvolumeofdistributionare0.64h,210μg×h/mL,7.93mL/min/kg,and0.44L/kg,respectively[1].2-PMPAat250mg/kg,inananesthetizedmouse,afteraninitialrise,producesarapiddeclineandastrikingattenuationinBOLDsignalsingraymatter.Thesignatureof2-PMPAonbrainT2*signalsingraymatteratboth167and250mg/kgincludesasignificantinitialriselastingseveralminutes[3].2-PMPAhasneuroprotectiveactivityinananimalmodelofstrokeandanti-allodynicactivityinCCImodel.Administrationof2-PMPA(50mg/kg)producesameanpeakconcentrationof2-PMPAof29.66±8.1μM.Thisconcentrationisabout100,000foldmorethanisneededforinhibitionofNAAGpeptidase,andindicatesverygoodpenetrationtothebrain.Administrationof50mg/kg2-PMPA(i.p.)producesacontinuouslyincreasingextracellularNAAGconcentration,whichstartesdirectlyafterapplication[4].PROTOCOLCellAssay[2]Neuronalculturesandneuron–gliamixedculturesaretreatedwithketaminedilutedintheculturemedium(1,3,10,30,100,300,1000,2000,3000μM)for24htocompareneurotoxicityinthesetwodifferentcellcultures.2-PMPAisselectedtoexploretheprotectiveeffectonketamine-inducedneurotoxicityinthesetwodifferentcellcultures.Cellsareexposedto2-PMPA(20,50,100μM)halfanhourbefore10μMketaminetreatmentinneuronalculturesand2mMketaminetreatmentinneuron–gliamixedculturesfor24h.Differentdosesofketaminechoseninneuronalculturesandneuron–gliamixedculturesarebasedontheresultsofcellviabilitytests[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRats:2-PMPAisdissovledinmethanolanddilutedinacetonitrile/water(1:1,v/v).TheconcentrationofstockAdministration[1][3]solutionis1mg/mL.MaleWistarratsareusedinthestudy.2-PMPAisadministeredtomaleWistarratsasasingleintraperitoneal(i.p.)dose.At0.08,0.25,0.5,1,2,and4hpostdose,bloodsamplesarecollectedinheparinizedmicrotubesbycardiacpunctureimmediatelybeforesacrifice.Tissues(brains,sciaticnervesand2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDRG’s)aredissectedafterexsanguinationandimmediatelyflashfrozen(-80°C).Plasmaispreparedbycentrifugationimmediatelyaftercollectionofbloodsamples.2-PMPAisassayedinplasmaandtissuesbythedevelopedLC/MS/MSmethod[1].Mice:MaleSwiss-Webster(SW)miceareusedinthestudy.Theeffectof2-PMPAistestedonanarbitrarilyselectedexperimentalgroupof12mice(groupB)byinjectingthedrugintraperitoneally(i.p.)at80mg/kg.Thecontrolgroup(groupA)isinjectedi.p.withthewatervehicle.Rotarodtestsarethenperformedatadditionaltimesof70,240,420,and1440minpostinjection,andperformanceismeasuredaslatencytofall,inseconds,atthetestedrpm.Atotalof4802-minRotarodtestsareperformedinthisexperiment[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ACSNano.2021Apr27;15(4):7179-7194.?JMedChem.2021Mar30.?BiochemBiophysResCommun.2020Dec17;533(4):1393-1399.?GhentUniversity.MasterofScienceinPharmaceuticalCare.2021Mar.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RaisR,etal.BioanalyticalmethodforevaluatingthepharmacokineticsoftheGCP-IIinhibitor2-phosphonomethylpentanedioicacid(2-PMPA).JPharmBiomedAnal.2014Jan;88:162-9.[2].ZuoD,etal.Existenceofgliamitigatedketamine-inducedneurotoxicityinneuron-gliamixedculturesofneonatalratcortexandtheglia-mediatedprotectiveeffectof2-PMPA.Neurotoxicology.2