| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
PMPA free acid targets glutamate carboxypeptidase II (GCPII), also known as NAALADase (N-acetylated α-linked dipeptidase). GCPII is a metalloprotease that catabolizes the abundant neuropeptide N-acetylaspartylglutamate (NAAG) to N-acetylaspartate (NAA) and glutamate. Inhibition of GCPII increases NAAG levels and decreases glutamate levels, which has implications for neuroprotection, addiction, and pain.
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| ln Vitro |
2-PMPA is a strong and specific GCPII inhibitor that catabolizes the neuropeptide N-acetylaspartylglutamate (NAAG), which is widely distributed, into N-acetylaspartate (NAA) and glutamine acid enzyme. 2. In numerous animal models of neurological disorders, 2-PMPA shows significant efficacy. 2. The analysis of biological matrices is severely hampered by 2-PMPA, a highly polar compound with numerous negative charges [1]. 2. In mixed cultures, PMPA mitigates the ketamine-induced reduction in cell viability and elevation in LDH levels, but not in neuronal cultures [2].
PMPA free acid demonstrates potent inhibition of GCPII/NAALADase with an IC50 of 300 pM. This makes it one of the most potent GCPII inhibitors known. Its high potency and selectivity have been characterized in enzymatic assays. The compound's ability to inhibit NAAG hydrolysis and modulate glutamate levels has been confirmed in vitro. Its activity is assessed by measuring NAAG hydrolysis or glutamate production in enzyme preparations or tissue homogenates. |
| ln Vivo |
The maximal plasma concentration was observed after 0.25 hours following intraperitoneal dose of 100 mg/kg 2-PMPA, which was 275 μg/mL. The distribution volume, apparent clearance rate, half-life, area under the curve, and 7.93 mL/min/kg are, in that order, 0.44 L/kg, 210 μg×h/mL, and 0.64 h, respectively [1]. Following an initial increase in 2-PMPA at a dose of 250 mg/kg in mice under anesthesia, the gray matter BOLD signal rapidly declined and became much weaker. The gray matter brain T2* signals exhibit notable initial rises lasting several minutes at 167 and 250 mg/kg of 2-PMPA [3]. 2. In animal models of stroke and CCI, 2-PMPA has neuroprotective and anti-allodynia effects. A mean peak 2-PMPA concentration of 29.66±8.1 μM was obtained with administration of 50 mg/kg of 2-PMPA. This concentration shows great brain penetration, as it is around 100,000 times more than what is needed to inhibit NAAG peptidase. After 50 mg/kg 2-PMPA (ip) is administered, extracellular NAAG concentrations rise steadily and start to rise right away [4].
PMPA free acid has been studied in vivo for its neuroprotective effects. By inhibiting GCPII, it increases NAAG levels and decreases glutamate levels, which can protect against excitotoxicity. It has been investigated in models of neuropathic pain, stroke, traumatic brain injury, and drug addiction. The compound's ability to cross the blood-brain barrier and its in vivo efficacy have been demonstrated in preclinical studies. Detailed efficacy data are available in the literature. |
| Enzyme Assay |
GCPII enzyme inhibition assays are performed using recombinant human GCPII enzyme or membrane preparations from tissues expressing GCPII (e.g., prostate, brain). The enzyme is incubated with the substrate NAAG or a fluorogenic substrate (e.g., Z-Glu-Tyr-AMC) in assay buffer (50 mM Tris-HCl pH 7.4, 100 mM NaCl). Hydrolysis of the substrate releases glutamate or a fluorescent product, which is quantified by HPLC, LC-MS, or fluorescence. Test compounds are serially diluted and added to the reaction mixture. IC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate.
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| Cell Assay |
Cellular GCPII inhibition is evaluated in cell lines expressing GCPII (e.g., LNCaP prostate cancer cells) or in primary neuronal cultures. Cells are cultured in appropriate media and treated with PMPA free acid at various concentrations (0.1-100 nM). NAAG hydrolysis is measured by quantifying NAAG and glutamate levels in the culture medium by HPLC or LC-MS. Cell viability is assessed using MTT or LDH assays. Each experiment includes known GCPII inhibitors as positive controls and vehicle controls.
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| Animal Protocol |
In vivo studies are conducted in rodent models of neuropathic pain, stroke, traumatic brain injury, or drug addiction. PMPA free acid is administered intraperitoneally, intravenously, or intracerebroventricularly at doses typically ranging from 0.1-10 mg/kg. Behavioral assessments include pain sensitivity (von Frey test, hot plate), motor function, and addiction-related behaviors. Brain tissue is collected for neurochemical analysis (NAAG and glutamate levels by HPLC or LC-MS) and histology. Sample sizes typically range from 8-12 animals per group.
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| ADME/Pharmacokinetics |
PMPA free acid has a molecular weight of 226.12 g/mol and a molecular formula of C6H11O7P. Solubility: DMSO. Purity: ≥97-98% by HPLC. Chemical name: 2-(phosphonomethyl)pentanedioic acid. Storage: typically at -20°C. Bioavailability, half-life, and tissue distribution data are available from preclinical studies. It has limited oral bioavailability and is typically administered parenterally.
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| Toxicity/Toxicokinetics |
PMPA free acid has been evaluated in preclinical toxicology studies. It is generally well-tolerated at therapeutic doses. Standard toxicology studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on the central nervous system. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References |
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| Additional Infomation |
PMPA free acid is also known as 2-PMPA and 2-(Phosphonomethyl)pentanedioic acid. It is a potent and selective GCPII/NAALADase inhibitor with an IC50 of 300 pM. It catabolizes the neuropeptide NAAG to NAA and glutamate. It has been studied for neuroprotection, pain, and addiction. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C6H11O7P
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|---|---|
| Molecular Weight |
226.121103525162
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| Exact Mass |
226.024
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| CAS # |
173039-10-6
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| Related CAS # |
373645-42-2 (sodium);173039-10-6 (free acid);
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| PubChem CID |
10130754
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| Appearance |
Light yellow to yellow ointment
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
538.8±60.0 °C at 760 mmHg
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| Flash Point |
279.6±32.9 °C
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| Vapour Pressure |
0.0±3.1 mmHg at 25°C
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| Index of Refraction |
1.541
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| LogP |
-2.85
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
14
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| Complexity |
267
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(CCC(CP(=O)(O)O)C(=O)O)=O
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| InChi Key |
ISEYJGQFXSTPMQ-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
2-(phosphonomethyl)pentanedioic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ≥ 28 mg/mL (~123.83 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (442.24 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4224 mL | 22.1122 mL | 44.2243 mL | |
| 5 mM | 0.8845 mL | 4.4224 mL | 8.8449 mL | |
| 10 mM | 0.4422 mL | 2.2112 mL | 4.4224 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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