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MedKoo Cat#: 530517 | Name: PMPA free acid
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PMPA is a NAALADase inhibitor. PMPA increases threshold for electroconvulsions and enhances the antiseizure action of valproate against maximal electroshock-induced seizures in mice. Inhibition of NAALADase by 2-PMPA attenuates cocaine-induced relapse in rats: a NAAG-mGluR2/3-mediated mechanism. PMPA attenuates magnetic resonance BOLD signals in brain of anesthetized mice: evidence of a link between neuron NAAG release and hyperemia.

Chemical Structure

PMPA free acid
PMPA free acid
CAS#173039-10-6 (free acid)

Theoretical Analysis

MedKoo Cat#: 530517

Name: PMPA free acid

CAS#: 173039-10-6 (free acid)

Chemical Formula: C6H11O7P

Exact Mass: 226.0242

Molecular Weight: 226.12

Elemental Analysis: C, 31.87; H, 4.90; O, 49.53; P, 13.70

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
10mg USD 125.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 425.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,350.00 Ready to ship
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Related CAS #
373645-42-2 (sodium) 173039-10-6 (free acid)
Synonym
PMPA, NAALADase inhibitor; PMPA sodium
IUPAC/Chemical Name
2-(phosphonomethyl)pentanedioic acid
InChi Key
ISEYJGQFXSTPMQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C6H11O7P/c7-5(8)2-1-4(6(9)10)3-14(11,12)13/h4H,1-3H2,(H,7,8)(H,9,10)(H2,11,12,13)
SMILES Code
O=C(O)C(CP(O)(O)=O)CCC(O)=O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
2-PMPA is a potent and selective inhibitor of glutamate carboxypeptidase II (GCPII) with an IC50 of 300 pM.
In vitro activity:
2-PMPA was applied to the cell cultures to determine the efficacy of this NAAG peptidase inhibitor in reducing ketamine-induced neurotoxicity. As shown in Fig. 9A, the neurotoxic effects of ketamine (2 mM) were significantly attenuated by 2-PMPA (100 μM) when the drug was co-incubated for 24 h in neuron–glia mixed cultures (p < 0.05). However, the decrease of cell viability induced by ketamine (10 μM) was not significantly attenuated by coincubation with 2-PMPA (20, 50, 100 μM) in neuronal cultures (Fig. 9B, p > 0.05). The morphological changes of neurons and astrocytes in response to 2-PMPA against ketamine induced neurotoxicity was assessed in the mixed cultures and neuronal cultures using Rosenfield's staining (Fig. 10, Fig. 11, respectively). As shown in Fig. 10A, neurons and astrocytes in the mixed cultures of vehicle control group grew in good condition. After treatment with 2 mM ketamine for 24 h, the cell bodies of astrocytes were shrunken and cytoplasmic vacuoles appeared. Neurites of neurons disappeared and cell bodies were swollen (Fig. 10B). The number of neuronal nodes in the ketamine group was significantly lower than that in the vehicle control group (Fig. 10G, p < 0.05). 2-PMPA (100 μM) alone had no apparent influence on neuron and astrocyte morphology (Fig. 10C). Treatment with 2-PMPA (20 and 50 μM, Fig. 10D, E and G, respectively) for 24 h did not mitigate the damage of neurons and astrocytes induced by ketamine. While treatment with 2-PMPA (100 μM) for 24 h, the damage of astrocytes induced by ketamine was not improved, but the neuron morphology was improved, and neurite extension and apparent cross linking was retained (Fig. 10F). Reference: Neurotoxicology. 2014 Sep;44:218-30. https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(14)00093-X
In vivo activity:
The NAAG peptidase inhibitor 2-PMPA (2-(phosphonomethyl)pentanedioic acid) had neuroprotective activity in an animal model of stroke and anti-allodynic activity in CCI model despite its uncertain ability to penetrate the blood-brain barrier. The NAAG concentration in brain ECF under basal conditions and its alteration in relation to the brain ECF concentration of 2-PMPA is unclear. We therefore assessed those brain concentrations after i.p. administration of 2-PMPA, using in vivo microdialysis combined with LC/MS/MS analysis. Administration of 2-PMPA (50mg/kg) produced a mean peak concentration of 2-PMPA of 29.66+/-8.1microM. This concentration is about 100,000 fold more than is needed for inhibition of NAAG peptidase, and indicates very good penetration to the brain. Application of 2-PMPA was followed by a linear increase of NAAG-concentration reaching a maximum of 2.89+/-0.42microM at the end of microdialysis. However, during the time the anti-allodynic effects of 2-PMPA were observed, the NAAG concentration in the ECF did not reach levels which are likely to have an impact on any known target. It appears therefore that the observed behavioural effects of 2-PMPA may not be mediated by NAAG nor, in turn, by mGluR3 receptors. Reference: Neuropharmacology. 2006 Dec;51(7-8):1163-71. https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(06)00227-9
Solvent mg/mL mM comments
Solubility
Water 20.0 88.40
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 226.12 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
1. Zuo D, Wang C, Li Z, Lin L, Duan Z, Qi H, Li L, Sun F, Wu Y. Existence of glia mitigated ketamine-induced neurotoxicity in neuron-glia mixed cultures of neonatal rat cortex and the glia-mediated protective effect of 2-PMPA. Neurotoxicology. 2014 Sep;44:218-30. doi: 10.1016/j.neuro.2014.06.002. Epub 2014 Jun 12. PMID: 24931484.
In vivo protocol:
1. Nagel J, Belozertseva I, Greco S, Kashkin V, Malyshkin A, Jirgensons A, Shekunova E, Eilbacher B, Bespalov A, Danysz W. Effects of NAAG peptidase inhibitor 2-PMPA in model chronic pain - relation to brain concentration. Neuropharmacology. 2006 Dec;51(7-8):1163-71. doi: 10.1016/j.neuropharm.2006.07.018. Epub 2006 Aug 22. PMID: 16926034.
1: Majer P, Jančařík A, Krečmerová M, Tichý T, Tenora L, Wozniak K, Wu Y, Pommier E, Ferraris D, Rais R, Slusher BS. Discovery of Orally Available Prodrugs of the Glutamate Carboxypeptidase II (GCPII) Inhibitor 2-Phosphonomethylpentanedioic Acid (2-PMPA). J Med Chem. 2016 Mar 24;59(6):2810-9. doi: 10.1021/acs.jmedchem.6b00062. PubMed PMID: 26930119. 2: Rais R, Rojas C, Wozniak K, Wu Y, Zhao M, Tsukamoto T, Rudek MA, Slusher BS. Bioanalytical method for evaluating the pharmacokinetics of the GCP-II inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA). J Pharm Biomed Anal. 2014 Jan;88:162-9. doi: 10.1016/j.jpba.2013.08.028. PubMed PMID: 24055700; PubMed Central PMCID: PMC3891469. 3: Lee SK, Kim H, Cheong YH, Kim MJ, Jo SA, Youn HS, Park SI. S1 pocket of glutamate carboxypeptidase II: a new binding site for amyloid-β degradation. Biochem Biophys Res Commun. 2013 Sep 6;438(4):765-71. doi: 10.1016/j.bbrc.2013.07.059. PubMed PMID: 23891752. 4: Popik P, Kozela E, Wróbel M, Wozniak KM, Slusher BS. Morphine tolerance and reward but not expression of morphine dependence are inhibited by the selective glutamate carboxypeptidase II (GCP II, NAALADase) inhibitor, 2-PMPA. Neuropsychopharmacology. 2003 Mar;28(3):457-67. PubMed PMID: 12629525. 5: Tallarida C, Song K, Raffa RB, Rawls SM. Glutamate carboxypeptidase II (GCPII) inhibitor displays anti-glutamate and anti-cocaine effects in an invertebrate assay. Amino Acids. 2012 Jun;42(6):2521-4. doi: 10.1007/s00726-011-1052-6. PubMed PMID: 21850438; PubMed Central PMCID: PMC3265618. 6: Rais R, Wozniak K, Wu Y, Niwa M, Stathis M, Alt J, Giroux M, Sawa A, Rojas C, Slusher BS. Selective CNS Uptake of the GCP-II Inhibitor 2-PMPA following Intranasal Administration. PLoS One. 2015 Jul 7;10(7):e0131861. doi: 10.1371/journal.pone.0131861. PubMed PMID: 26151906; PubMed Central PMCID: PMC4494705. 7: Tiffany CW, Cai NS, Rojas C, Slusher BS. Binding of the glutamate carboxypeptidase II (NAALADase) inhibitor 2-PMPA to rat brain membranes. Eur J Pharmacol. 2001 Sep 14;427(2):91-6. PubMed PMID: 11557259. 8: Mesters JR, Henning K, Hilgenfeld R. Human glutamate carboxypeptidase II inhibition: structures of GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA. Acta Crystallogr D Biol Crystallogr. 2007 Apr;63(Pt 4):508-13. PubMed PMID: 17372356. 9: Xi ZX, Li X, Peng XQ, Li J, Chun L, Gardner EL, Thomas AG, Slusher BS, Ashby CR Jr. Inhibition of NAALADase by 2-PMPA attenuates cocaine-induced relapse in rats: a NAAG-mGluR2/3-mediated mechanism. J Neurochem. 2010 Jan;112(2):564-76. doi: 10.1111/j.1471-4159.2009.06478.x. PubMed PMID: 19895667; PubMed Central PMCID: PMC2809121. 10: Ha D, Bing SJ, Ahn G, Kim J, Cho J, Kim A, Herath KH, Yu HS, Jo SA, Cho IH, Jee Y. Blocking glutamate carboxypeptidase II inhibits glutamate excitotoxicity and regulates immune responses in experimental autoimmune encephalomyelitis. FEBS J. 2016 Sep;283(18):3438-56. doi: 10.1111/febs.13816. PubMed PMID: 27444540. 11: Luszczki JJ, Mohamed M, Czuczwar SJ. 2-phosphonomethyl-pentanedioic acid (glutamate carboxypeptidase II inhibitor) increases threshold for electroconvulsions and enhances the antiseizure action of valproate against maximal electroshock-induced seizures in mice. Eur J Pharmacol. 2006 Feb 15;531(1-3):66-73. PubMed PMID: 16403497. 12: Thomas AG, Liu W, Olkowski JL, Tang Z, Lin Q, Lu XC, Slusher BS. Neuroprotection mediated by glutamate carboxypeptidase II (NAALADase) inhibition requires TGF-beta. Eur J Pharmacol. 2001 Oct 26;430(1):33-40. PubMed PMID: 11698060. 13: Pomper MG, Musachio JL, Zhang J, Scheffel U, Zhou Y, Hilton J, Maini A, Dannals RF, Wong DF, Kozikowski AP. 11C-MCG: synthesis, uptake selectivity, and primate PET of a probe for glutamate carboxypeptidase II (NAALADase). Mol Imaging. 2002 Apr-Jun;1(2):96-101. PubMed PMID: 12920850. 14: Kozela E, Wrobel M, Kos T, Wojcikowski J, Daniel WA, Wozniak KM, Slusher BS, Popik P. 2-MPPA, a selective glutamate carboxypeptidase II inhibitor, attenuates morphine tolerance but not dependence in C57/Bl mice. Psychopharmacology (Berl). 2005 Dec;183(3):275-84. PubMed PMID: 16220328. 15: Barinka C, Rovenská M, Mlcochová P, Hlouchová K, Plechanovová A, Majer P, Tsukamoto T, Slusher BS, Konvalinka J, Lubkowski J. Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II. J Med Chem. 2007 Jul 12;50(14):3267-73. PubMed PMID: 17567119. 16: Peng XQ, Li J, Gardner EL, Ashby CR Jr, Thomas A, Wozniak K, Slusher BS, Xi ZX. Oral administration of the NAALADase inhibitor GPI-5693 attenuates cocaine-induced reinstatement of drug-seeking behavior in rats. Eur J Pharmacol. 2010 Feb 10;627(1-3):156-61. doi: 10.1016/j.ejphar.2009.10.062. PubMed PMID: 19887067; PubMed Central PMCID: PMC2819210. 17: Urazaev AK, Grossfeld RM, Lieberman EM. Regulation of glutamate carboxypeptidase II hydrolysis of N-acetylaspartylglutamate (NAAG) in crayfish nervous tissue is mediated by glial glutamate and acetylcholine receptors. J Neurochem. 2005 May;93(3):605-10. PubMed PMID: 15836619. 18: Zuo D, Wang C, Li Z, Lin L, Duan Z, Qi H, Li L, Sun F, Wu Y. Existence of glia mitigated ketamine-induced neurotoxicity in neuron-glia mixed cultures of neonatal rat cortex and the glia-mediated protective effect of 2-PMPA. Neurotoxicology. 2014 Sep;44:218-30. doi: 10.1016/j.neuro.2014.06.002. PubMed PMID: 24931484. 19: Lukawski K, Kamiński RM, Czuczwar SJ. Effects of selective inhibition of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) on mice in learning and memory tasks. Eur J Pharmacol. 2008 Jan 28;579(1-3):202-7. PubMed PMID: 18031726. 20: Rong SB, Zhang J, Neale JH, Wroblewski JT, Wang S, Kozikowski AP. Molecular modeling of the interactions of glutamate carboxypeptidase II with its potent NAAG-based inhibitors. J Med Chem. 2002 Sep 12;45(19):4140-52. PubMed PMID: 12213057.