WWL 70
目录号 : GC15074
A selective inhibitor of ABHD6
Cas No.:947669-91-2
Sample solution is provided at 25 µL, 10mM.
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WWL70 is a selective alpha/beta hydrolase domain 6 (ABHD6) inhibitor with an IC50 of 70 nM.
At 1 h after WWL70 (10 μM) treatment, 2-Arachidonoylglycerol (2-AG) is increased by 20% compare to untreated cells. At either 1 or 10 μM, WWL70 completely blocks the lipopolysaccharide (LPS)-induced increase of PGE2. The enhanced mRNA expression of mPGES-1 and mPGES-2 by LPS is also reduced by WWL70. The IC50 of WWL70 to inhibit the PGE2 biosynthesis is about 100 nM[2].
Although post-treatment with WWL70 at 5 mg/kg does not have any effect, treatment with WWL70 at 10 mg/kg improves the performance significantly. WWL70 treatment improves motor coordination of traumatic brain injury (TBI) mice in a concentration dependent manner. The latency to fall in animals treated with WWL70 at 5 mg/kg increases from 74.92±4.8 to 99.57±5.21 on day 3 (p<0.01) and from 87.32±4.42 to 100.14±3.56 on day 7 (p<0.05) post-injury when compare with the vehicle-TBI groups. At 10 mg/kg, WWL70 treatment improves motor coordination starting on day 1 post-injury. WWL70 treatment completely restores the ability of TBI mice to continuously alternate arms during Y maze exploration (69.67±4.98 %)[3].
References:
[1]. Li W, et al. A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases. J Am Chem Soc. 2007 Aug 8;129(31):9594-5.
[2]. Tanaka M, et al. WWL70 attenuates PGE2 production derived from 2-arachidonoylglycerol in microglia by ABHD6-independent mechanism. J Neuroinflammation. 2017 Jan 10;14(1):7.
[3]. Tchantchou F, et al. Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury. J Neurotrauma. 2013 Apr 1;30(7):565-79.
| Cell experiment[1]: | |
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Cell lines |
HEK293 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 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
10 μM, 10 min |
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Applications |
Depolarization-induced suppression of excitation (DSE) is a major form of cannabinoid-mediated short-term retrograde neuronal plasticity and is found in numerous brain regions. ABHD6 is not present presynaptically in autaptic neurons and the ABHD6 inhibitor, WWL70, has no effect on the autaptic DSE time course. |
| Animal experiment[1]: | |
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Animal models |
Male C57BL/6 mice, 25–30 g |
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Dosage form |
WWL70 (5 mg/kg or 10 mg/kg) dissolved in 1% DMSO in physiologic saline was injected intraperitoneally 30 min after TBI, and then once a day for ≥ 7 days depending on the experimental design. |
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Applications |
WWL70, a selective ABHD6 inhibitor, improved motor coordination and working memory performance. WWL70 treatment reduced lesion volume in the cortex and neurodegeneration in the dendate gyrus. It also suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2 and enhanced the expression of arginase-1 in the ipsilateral cortex at 3 and 7 days post-TBI, suggesting microglia/macrophages shifted from M1 to M2 phenotypes after treatment. The blood-brain barrier dysfunction at 3 and 7 days post-TBI was dramatically reduced. Furthermore, the beneficial effects of WWL70 involved up-regulation and activation of cannabinoid type 1 and type 2 receptors and were attributable to the phosphorylation of the extracellular signal regulated kinase and the serine/threonine protein kinase AKT. |
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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. Straiker A1, Hu SS, Long JZ et al. Monoacylglycerol lipase limits the duration of endocannabinoid-mediated depolarization-induced suppression of excitation in autaptic hippocampal neurons. Mol Pharmacol. 2009 Dec;76(6):1220-7. 2. Tchantchou F1, Zhang Y. Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury. J Neurotrauma. 2013 Apr 1;30(7):565-79. |
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| Cas No. | 947669-91-2 | SDF | |
| 化学名 | 4'-carbamoyl-[1,1'-biphenyl]-4-yl methyl(3-(pyridin-4-yl)benzyl)carbamate | ||
| Canonical SMILES | O=C(N(C)CC1=CC=CC(C2=CC=NC=C2)=C1)OC3=CC=C(C=C3)C4=CC=C(C(N)=O)C=C4 | ||
| 分子式 | C27H23N3O3 | 分子量 | 437.49 |
| 溶解度 | ≥ 14.45mg/mL in DMSO | 储存条件 | Store 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 | 2.2858 mL | 11.4288 mL | 22.8577 mL |
| 5 mM | 0.4572 mL | 2.2858 mL | 4.5715 mL |
| 10 mM | 0.2286 mL | 1.1429 mL | 2.2858 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet