2-PMPA-2-Phosphonomethyl-pentanedioic-acid-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemE2-PMPACat.No.:HY-100788CASNo.:173039-10-6Synonyms:2-(Phosphonomethyl)pentanedioicacid分⼦式:C₆H₁₁O₇P分⼦量:226.12作⽤靶点:Carboxypeptidase作⽤通路:MetabolicEnzyme/Protease储存⽅式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性数据体外实验H2O:≥28mg/mL(123.83mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM4.4224mL22.1122mL44.2243mL5mM0.8845mL4.4224mL8.8449mL10mM0.4422mL2.2112mL4.4224mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(storedundernitrogen)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：PBS1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:100mg/mL(442.24mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性2-PMPA⾼效选择性的⾕氨酸羧肽酶II(GCPII)抑制剂，IC50值为300pM。IC50&TargetIC50:300pM(GCPII)[1]体外研究2-PMPAisapotentandselectiveinhibitorofGCPII,anenzymewhichcatabolizestheabundantneuropeptideN-acetyl-aspartyl-glutamate(NAAG)toN-acetylaspartate(NAA)andglutamate.2-PMPAdemonstratesrobustefficacyinnumerousanimalmodelsofneurologicaldisease.2-PMPAisahighlypolarcompoundwithmultiplenegativechargescausingsignificantchallengesforanalysisinbiologicalmatrices[1].2-PMPAreducesketamine-induceddecreaseofcellviabilityandincreaseofLDHlevelsinthemixedculturesbutnotintheneuronalcultures[2].体内研究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—您⾝边的抑制剂⼤师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.户使⽤本产品发表的科研⽂献•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