DL-TBOA
(Synonyms: DL-threo-β-Benzyloxyaspartate) 目录号 : GC16670
An EAAT inhibitor
Cas No.:205309-81-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Inhibitory activities |
DL-threo-b-Benzyloxyaspartate (DL-TBOA) was synthesized and examined as an inhibitor of sodium-dependent glutamate/aspartate (excitatory amino acid) transporters. DL-TBOA inhibited the uptake of glutamate in COS-1 cells expressing the human excitatory amino acid transporter-1 (EAAT1) (Ki=42 mM). With regard to the human excitatory amino acid transporter-2(EAAT2), the Ki of DL-TBOA 5.7 mM. |
| Cell experiment [1]: | |
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Cell lines |
COS-1 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
Measurements of glutamate uptake in transfected COS-1 cells assey: 37℃ for 12 min. |
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Applications |
DL-TBOA markedly inhibited glutamate (1 mM) uptake in transfected cells in a dosedependent manner. The subconfluent cells were washed two times with 300 μl of modified phosphate-buffered saline that contained 137 mM NaCl, 2.7 mM KCl, 8.1 mM Na2HPO4, 1.5 mM KH2PO4,1mM MgCl2, 1mM CaCl2, and 10 mM D-glucose, pH 7.4, and preincubated in 300 μl of the same buffer at 37℃ for 12 min. After aspiration of the buffer, cells were incubated with 1 μM L-glutamate in 100 μl of modified phosphate-buffered saline in the absence or presence of DL-TBOA at various concentrations at 37℃ for 12 min. |
| Animal experiment [2]: | |
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Animal models |
Males Wistar rats |
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Dosage form |
500 μM DL-TBOA |
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Preparation method |
Dissolved in Ringer Krebs medium which containing (in mM): NaCl 118, KCl 4.5, MgSO4 1.18, KH2PO4 1.2, CaCl2 2.5, NaHCO3 25. |
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Application |
Microdialysis administration of 500μM DL-TBOA into the hippocampus increased 3.4- and nine-fold the extracellular levels of aspartate and glutamate, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. KEIKO SHIMAMOTO, BRUNO LEBRUN, YOSHIMI YASUDA-KAMATANI, at al. DL-threo-b-Benzyloxyaspartate, A Potent Blocker of Excitatory Amino Acid Transporters. MOLECULAR PHARMACOLOGY, 53:195–201 (1998). [2]. T. MONTIEL,A. CAMACHO,A. M. ESTRADA-S?NCHEZ AND L. MASSIEU. DIFFERENTIAL EFFECTS OF THE SUBSTRATE INHIBITOR L-TRANSPYRROLIDINE-2,4-DICARBOXYLATE (PDC) AND THE NON-SUBSTRATE INHIBITOR DL-THREO-β-BENZYLOXYASPARTATE (DL-TBOA) OF GLUTAMATE TRANSPORTERS ON NEURONAL DAMAGE AND EXTRACELLULAR AMINO ACID LEVELS IN RAT BRAIN IN VIVO. Neuroscience 133 (2005) 667–678. | |
Ki: 42 μM for EAAT1; 5.7 μM for EAAT2
Glutamate acts as an excitatory neurotransmitter in the mammalian central nervous system and a potent neurotoxin. Glutamate transporters also play an important role in maintaining the extracellular glutamate concentration below neurotoxic levels and therefore contribute to the prevention of neuronal damage. DL-TBOA was synthesized and examined as an inhibitor of sodium-dependent glutamate/aspartate transporters(excitatory amino acid transporters).
In vitro: DL-TBOA inhibited the uptake of [14C]glutamate in COS-1 cells overexpressing the human excitatory amino acid transporter-1 (EAAT1) (Ki = 42 μM) with almost the same potency as DL-threo-b-hydroxyaspartate (Ki = 58 μM). With regard to the human excitatory amino acid transporter-2 (EAAT2), the inhibitory effect of DL-TBOA (Ki = 5.7 μM) was much more potent than that of dihydrokainate (Ki = 79 μM), which is well known as a selective blocker of this subtype. [1].
In vivo: Microdialysis administration of 500 μM DL-TBOA into the hippocampus increased 3.4- and nine-fold the extracellular levels of aspartate and glutamate, respectively. Upon stereotaxic administration it induced neuronal damage dose-dependently in CA1 and dentate gyrus, and convulsive behavior. Electroencephalographic recording showed limbic seizures appearance in the hippocampus after DL-TBOA infusion. [2].
Clinical trial: Up to now, DL-TBOA is still in the preclinical development stage.
Reference:
[1] Shimamoto K, Lebrun B, Yasuda-Kamatani Y, Sakaitani M, Shigeri Y, Yumoto N, Nakajima T. DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. Mol Pharmacol. 1998 Feb;53(2):195-201.
[2] Montiel T, Camacho A, Estrada-Sánchez AM, Massieu L. Differential effects of the substrate inhibitor l-trans-pyrrolidine-2,4-dicarboxylate (PDC) and the non-substrate inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA) of glutamate transporters on neuronal damage and extracellular amino acid levels in rat brain in vivo. Neuroscience. 2005;133(3):667-78.
| Cas No. | 205309-81-5 | SDF | |
| 别名 | DL-threo-β-Benzyloxyaspartate | ||
| 化学名 | (2S,3S)-2-amino-3-(benzyloxy)succinic acid | ||
| Canonical SMILES | OC([C@H]([C@@H](C(O)=O)N)OCC1=CC=CC=C1)=O | ||
| 分子式 | C11H13NO5 | 分子量 | 239.23 |
| 溶解度 | <23.92mg/ml in DMSO | 储存条件 | Desiccate at -20°C |
| 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 | 4.1801 mL | 20.9004 mL | 41.8008 mL |
| 5 mM | 0.836 mL | 4.1801 mL | 8.3602 mL |
| 10 mM | 0.418 mL | 2.09 mL | 4.1801 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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