2-PMPA | CAS#173039-10-6 | Inhibitor

MedKoo Cat#: 145101 | Name: 2-PMPA

Description:

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

2-PMPA is a potent inhibitor of cytosolic carboxypeptidases. 2-PMPA efficiently inhibits CCP activities, including the deglutamylating activity of Nna1 on tubulin, with an IC50 of 0.21 mM, suggesting its potential as a leading compound targeting imbalanced polyglutamylation. 2-PMPA inhibits glutamate carboxypeptidase-II and reduces extracellular dopamine and glutamate levels in the NAc, suggesting its potential as a treatment for cocaine dependence.

Chemical Structure

2-PMPA

CAS#173039-10-6

Theoretical Analysis

MedKoo Cat#: 145101

Name: 2-PMPA

CAS#: 173039-10-6

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

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

Bulk Inquiry

Related CAS #

No Data

Synonym

2-PMPA; 2PMPA; 2 PMPA;

IUPAC/Chemical Name

2-(phosphonomethyl)pentanedioic acid

InChi Key

ISEYJGQFXSTPMQ-UHFFFAOYSA-N

InChi Code

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

OC(=O)CCC(CP(O)(O)=O)C(O)=O

Appearance

To be determined

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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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

Instruction

View handling instruction

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.

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

1: Wang R, Lin L, Zheng Y, Cao P, Yuchi Z, Wu HY. Identification of 2-PMPA as a novel inhibitor of cytosolic carboxypeptidases. Biochem Biophys Res Commun. 2020 Dec 17;533(4):1393-1399. doi: 10.1016/j.bbrc.2020.10.029. Epub 2020 Oct 20. PMID: 33092792. 2: Dash RP, Tichý T, Veeravalli V, Lam J, Alt J, Wu Y, Tenora L, Majer P, Slusher BS, Rais R. Enhanced Oral Bioavailability of 2-(Phosphonomethyl)-pentanedioic Acid (2-PMPA) from its (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl (ODOL)-Based Prodrugs. Mol Pharm. 2019 Oct 7;16(10):4292-4301. doi: 10.1021/acs.molpharmaceut.9b00637. Epub 2019 Sep 24. PMID: 31503493; PMCID: PMC7978038. 3: 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. Epub 2013 Aug 30. PMID: 24055700; PMCID: PMC3891469. 4: 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. Epub 2009 Nov 6. PMID: 19895667; PMCID: PMC2809121. 5: 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. 6: Hicks C, Gregg RA, Nayak SU, Cannella LA, Schena GJ, Tallarida CS, Reitz AB, Smith GR, Rawls SM. Glutamate carboxypeptidase II (GCPII) inhibitor 2-PMPA reduces rewarding effects of the synthetic cathinone MDPV in rats: a role for N-acetylaspartylglutamate (NAAG). Psychopharmacology (Berl). 2017 Jun;234(11):1671-1681. doi: 10.1007/s00213-017-4568-y. Epub 2017 Mar 1. PMID: 28251297; PMCID: PMC5433920. 7: 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. PMID: 26151906; PMCID: PMC4494705. 8: Zuo D, Wang C, Li Z, Lin L, Duan Z, Qi H, Li L, Sun F, Wu Y. Corrigendum to "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 44 (2014) 218-230]. Neurotoxicology. 2022 Jul;91:370-372. doi: 10.1016/j.neuro.2022.03.006. Epub 2022 Mar 29. Erratum for: Neurotoxicology. 2014 Sep;44:218-30. doi: 10.1016/j.neuro.2014.06.002. PMID: 35365354. 9: 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. Epub 2016 Mar 10. PMID: 26930119. 10: 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. Erratum in: Neurotoxicology. 2022 Jul;91:370-372. doi: 10.1016/j.neuro.2022.03.006. PMID: 24931484. 11: Baslow MH, Dyakin VV, Nowak KL, Hungund BL, Guilfoyle DN. 2-PMPA, a NAAG peptidase inhibitor, attenuates magnetic resonance BOLD signals in brain of anesthetized mice: evidence of a link between neuron NAAG release and hyperemia. J Mol Neurosci. 2005;26(1):1-15. doi: 10.1385/JMN:26:1:001. PMID: 15968081. 12: Fultz EK, Nei AYT, Chi JC, Lichter JN, Szumlinski KK. Effects of systemic pretreatment with the NAALADase inhibitor 2-PMPA on oral methamphetamine reinforcement in C57BL/6J mice. Front Psychiatry. 2024 Apr 4;15:1297275. doi: 10.3389/fpsyt.2024.1297275. PMID: 38638417; PMCID: PMC11024460. 13: Krečmerová M, Majer P, Rais R, Slusher BS. Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects. Front Chem. 2022 May 20;10:889737. doi: 10.3389/fchem.2022.889737. PMID: 35668826; PMCID: PMC9163707. 14: Tortella FC, Lin Y, Ved H, Slusher BS, Dave JR. Neuroprotection produced by the NAALADase inhibitor 2-PMPA in rat cerebellar neurons. Eur J Pharmacol. 2000 Aug 18;402(1-2):31-7. doi: 10.1016/s0014-2999(00)00519-7. PMID: 10940354. 15: 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. doi: 10.1016/s0014-2999(01)01236-5. PMID: 11557259. 16: Nedelcovych M, Dash RP, Tenora L, Zimmermann SC, Gadiano AJ, Garrett C, Alt J, Hollinger KR, Pommier E, Jančařík A, Rojas C, Thomas AG, Wu Y, Wozniak K, Majer P, Slusher BS, Rais R. Enhanced Brain Delivery of 2-(Phosphonomethyl)pentanedioic Acid Following Intranasal Administration of Its γ-Substituted Ester Prodrugs. Mol Pharm. 2017 Oct 2;14(10):3248-3257. doi: 10.1021/acs.molpharmaceut.7b00231. Epub 2017 Aug 31. PMID: 28763226; PMCID: PMC5795618. 17: Khacho P, Wang B, Bergeron R. The Good and Bad Sides of NAAG. Adv Pharmacol. 2016;76:311-49. doi: 10.1016/bs.apha.2016.01.003. Epub 2016 Mar 2. PMID: 27288081. 18: Vornov JJ, Hollinger KR, Jackson PF, Wozniak KM, Farah MH, Majer P, Rais R, Slusher BS. Still NAAG'ing After All These Years: The Continuing Pursuit of GCPII Inhibitors. Adv Pharmacol. 2016;76:215-55. doi: 10.1016/bs.apha.2016.01.007. Epub 2016 Mar 18. PMID: 27288079. 19: 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. doi: 10.1016/j.ejphar.2005.11.045. Epub 2006 Jan 3. PMID: 16403497. 20: Nonaka T, Yamada T, Ishimura T, Zuo D, Moffett JR, Neale JH, Yamamoto T. A role for the locus coeruleus in the analgesic efficacy of N-acetylaspartylglutamate peptidase (GCPII) inhibitors ZJ43 and 2-PMPA. Mol Pain. 2017 Jan;13:1744806917697008. doi: 10.1177/1744806917697008. PMID: 28326936; PMCID: PMC5407666.