PMPA (NAALADase inhibitor)
(Synonyms: 2-(Phosphonomethyl)pentanedioic acid) 目录号 : GC13467
A potent inhibitor of GCP II/NAALADase
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 | |
| 别名 | 2-(Phosphonomethyl)pentanedioic acid | ||
| 化学名 | 2-(phosphonomethyl)pentanedioic acid | ||
| Canonical SMILES | C(CC(=O)O)C(CP(=O)(O)O)C(=O)O | ||
| 分子式 | C6H11O7P | 分子量 | 226.12 |
| 溶解度 | PBS (pH 7.2): 10 mg/ml | 储存条件 | Store at -20°C, stored under nitrogen |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet