PMPA (NAALADase inhibitor) (Synonyms: 2-PMPA) |
| Catalog No.GC13467 |
A potent inhibitor of GCP II/NAALADase
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 173039-10-6
Sample solution is provided at 25 µL, 10mM.
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PMPA is a selective inhibitor of NAALADase with Ki value of 275 pM [1].
NAALADase also known as GCPII is a zinc metalloenzyme that resides in membranes and involves in the catalyzing process of neuropeptide NAAG to NAA and glutamate. It has been shown that NAALADase has the highest expression in nervous/ prostatic tissues and cancers and NAALADase inhibition produces a variety of effects on providing neuroprotection, detection, imaging and treatment of prostate cancer [2] [3].
PMPA is a potent NAALADase inhibitor and has a more activity than reported NAALADase inhibitor ZJ43. In male C57/Bl mice model, high doses of PMPA inhibited the morphine tolerance development (resembling the effect of 7.5 mg/kg of the NMDA receptor antagonist, memantine) while had no effect on severity of withdrawal; 100 mg/kg PMPA also significantly potentiated morphine withdrawal, but inhibited both acquisition and expression of morphine-induced conditioned place preference which suggested NAALADase involves in phenomena related to opioid addiction [4]. PMPA treatment increased the mice latency to enter the dark box during the training day and at the dose of 150 mg/kg PMPA treatment impaired spontaneous alternation and reduced locomotion in Y-maze task which demonstrated that PMPA affected mice learning and memory tasks through NAALADase inhibition [5].
References:
[1]. Tiffany, C.W., et al., Binding of the glutamate carboxypeptidase II (NAALADase) inhibitor 2-PMPA to rat brain membranes. Eur J Pharmacol, 2001. 427(2): p. 91-6.
[2]. Barinka, C., et al., Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer. Curr Med Chem, 2012. 19(6): p. 856-70.
[3]. Slusher, B.S., et al., Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury. Nat Med, 1999. 5(12): p. 1396-402.
[4]. Popik, P., et al., 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. 28(3): p. 457-67.
[5]. Lukawski, K., R.M. Kaminski, and S.J. Czuczwar, Effects of selective inhibition of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) on mice in learning and memory tasks. Eur J Pharmacol, 2008. 579(1-3): p. 202-7.
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Cell experiment: |
Neuronal cultures and neuron–glia mixed cultures are treated with ketamine diluted in the culture medium (1, 3, 10, 30, 100, 300, 1000, 2000, 3000 μM) for 24 h to compare neurotoxicity in these two different cell cultures. 2-PMPA is selected to explore the protective effect on ketamine-induced neurotoxicity in these two different cell cultures. Cells are exposed to 2-PMPA (20, 50, 100 μM) half an hour before 10 μM ketamine treatment in neuronal cultures and 2 mM ketamine treatment in neuron–glia mixed cultures for 24 h. Different doses of ketamine chosen in neuronal cultures and neuron–glia mixed cultures are based on the results of cell viability tests[2]. |
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Animal experiment: |
Rats: 2-PMPA is dissovled in methanol and diluted in acetonitrile/water (1:1, v/v). The concentration of stock solution is 1 mg/mL. Male Wistar rats are used in the study. 2-PMPA is administered to male Wistar rats as a single intraperitoneal (i.p.) dose. At 0.08, 0.25, 0.5, 1, 2, and 4 h post dose, blood samples are collected in heparinized microtubes by cardiac puncture immediately before sacrifice. Tissues (brains, sciatic nerves and DRG’s) are dissected after exsanguination and immediately flash frozen (-80°C). Plasma is prepared by centrifugation immediately after collection of blood samples. 2-PMPA is assayed in plasma and tissues by the developed LC/MS/MS method[1]. Mice: Male Swiss-Webster (SW) mice are used in the study. The effect of 2-PMPA is tested on an arbitrarily selected experimental group of 12 mice (group B) by injectingthe drug intraperitoneally (i.p.) at 80 mg/kg. The control group (group A) is injected i.p. with the water vehicle. Rotarod tests are then performed at additional times of 70, 240, 420, and 1440 min postinjection, and performance is measured as latency to fall, in seconds, at the tested rpm. A total of 480 2-min Rotarod tests are performed in this experiment[3]. |
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References: [1]. Rais R, et al. 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. |
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| Cas No. | 173039-10-6 | SDF | |
| Synonymes | 2-PMPA | ||
| Chemical Name | 2-(phosphonomethyl)pentanedioic acid | ||
| Canonical SMILES | C(CC(=O)O)C(CP(=O)(O)O)C(=O)O | ||
| Formula | C6H11O7P | M.Wt | 226.12 |
| Solubility | PBS (pH 7.2): 10 mg/ml | Storage | Store at -20°C, stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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