WWL 70 |
| Catalog No.GC15074 |
WWL 70은 IC50이 70nM인 선택적 알파/베타 가수분해효소 도메인 6(ABHD6) 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
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. |
|
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 | |
| Chemical Name | 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 | ||
| Formula | C27H23N3O3 | M.Wt | 437.49 |
| Solubility | ≥ 14.45mg/mL in DMSO | Storage | Store at -20°C |
| 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 | 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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
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