WWL 70 |
| Catalog No.GC15074 |
WWL 70 is a selective alpha/beta hydrolase domain 6 (ABHD6) inhibitor with an IC50 of 70nM.
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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WWL 70 is a selective alpha/beta hydrolase domain 6 (ABHD6) inhibitor with an IC50 of 70nM[1]. ABHD6 is a monoacylglycerol hydrolase that regulates lipid metabolism, neural signaling, synaptic plasticity, and immune-inflammatory responses through modulating the endocannabinoid system and AMPA receptor signaling, and its dysfunction is associated with obesity, neurodegenerative diseases, and psychiatric disorders[2][3]. WWL 70 plays an important role in relevant diseases research by inhibiting ABHD6[4][5].
In vitro, WWL 70(10μM, 15min) attenuated the expression of COX-2 and PGES-1/2 leading to the downregulation of the biosynthetic pathways of PGE2 and PGE2-G in LPS-activated mBV2 microglial cells via cannabinoid receptor-independent mechanisms[6].
In vivo,WWL 70 (10mg/kg/day) was intraperitoneally injected into APP/PS1 mice for 30 days, significantly decreasing Aβ levels and neuroinflammation in the hippocampus, enhancing Aβ phagocytosis by microglia, and improving synaptic plasticity and memory function of the mice[4]. Treatment with the selective ABHD6 inhibitor WWL 70(10mg/kg; 3h after surgery and then once daily until day 7; i.p.) significantly alleviated CCI-induced thermal hyperalgesia and mechanical allodynia, and reduced microglia activation, macrophage infiltration, and the production of nociceptive mediators in the ipsilateral lumbar spinal cord dorsal horn, DRG, and sciatic nerve in CCI-induced Neuropathic pain mice model[7].
References:
[1] Li, W., Blankman, J. L., & Cravatt, B. F. (2007). A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases. Journal of the American Chemical Society, 129(31), 9594–9595.
[2] Pusch, L. M., Riegler-Berket, L., Oberer, M., Zimmermann, R., & Taschler, U. (2022). α/β-Hydrolase Domain-Containing 6 (ABHD6)- A Multifunctional Lipid Hydrolase. Metabolites, 12(8), 761.
[3] Lau, D., Tobin, S., Pribiag, H., Nakajima, S., Fisette, A., Matthys, D., Franco Flores, A. K., Peyot, M. L., Murthy Madiraju, S. R., Prentki, M., Stellwagen, D., Alquier, T., & Fulton, S. (2024). ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice. Nature communications, 15(1), 10652.
[4] Xue, Z., Ye, L., Ge, J., Lan, Z., Zou, X., Mao, C., Bao, X., Yu, L., Xu, Y., & Zhu, X. (2023). Wwl70-induced ABHD6 inhibition attenuates memory deficits and pathological phenotypes in APPswe/PS1dE9 mice. Pharmacological research, 194, 106864.
[5] Bottemanne, P., Paquot, A., Ameraoui, H., Alhouayek, M., & Muccioli, G. G. (2019). The α/β-hydrolase domain 6 inhibitor WWL70 decreases endotoxin-induced lung inflammation in mice, potential contribution of 2-arachidonoylglycerol, and lysoglycerophospholipids. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(6), 7635–7646.
[6] Tanaka, M., Moran, S., Wen, J., Affram, K., Chen, T., Symes, A. J., & Zhang, Y. (2017). WWL70 attenuates PGE2 production derived from 2-arachidonoylglycerol in microglia by ABHD6-independent mechanism. Journal of neuroinflammation, 14(1), 7.
[7] Wen, J., Jones, M., Tanaka, M., Selvaraj, P., Symes, A. J., Cox, B., & Zhang, Y. (2018). WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms. Journal of neuroinflammation, 15(1), 9.
| Cell experiment [1]: | |
Cell lines | BV2 microglial cells |
Preparation Method | BV2 microglial cells were cultured in complete DMEM containing 5% heat-inactivated fetal bovine serum under humidified 5% CO2 environment. For PGE2 enzyme immunoassay, the cell culture medium was replaced with pre-warmed medium containing the ABHD6 inhibitor WWL 70 (10μM) and incubated for 15min. The cells were treated with 10μM of 2-AG for 15min, followed by addition of 100ng/ml LPS for BV2, or 2ng/ml LPS for primary microglia. After incubation for 18h, the culture medium was collected. Before addition to the enzyme linked immunoassay (EIA), the medium was centrifuged at 5000rpm for 2min with a table top centrifuge to exclude residual cells. |
Reaction Conditions | 10μM; 15min |
Applications | WWL 70 suppressed PGE2 production in LPS-activated microglia. |
| Animal experiment [2]: | |
Animal models | C57BL/6J mice |
Preparation Method | Mice were anesthetized with isoflurane (3.5% for induction and 2.0% for maintenance), and the mid to lower back of the animals along with the dorsal left thigh were shaved and cleaned with iodine and 75% ethanol. Using aseptic procedures, the common sciatic nerve was exposed at the mid-thigh level by blunt dissection. Under a dissection microscope, a nerve segment of 5mm long was separated from the surrounding tissues. Two ligatures of 6–0 sterile silk, spaced 1.0 to 1.5mm apart, were placed around the sciatic nerve. The ligatures were tied until they just constricted the diameter of the nerve, and a brief twitch was observed in the respective hind limb. In sham-operated mice, the sciatic nerve was isolated and exposed without ligation. The muscles and skins were closed with sutures. phor-saline (1:1:18), which was used as a vehicle control. CCI mice were randomly assigned to receive the ABHD6 inhibitor WWL 70 (10mg/kg) or the vehicle control. Drugs were given intraperitoneally (i.p.) 3h after surgery and then once daily until day 7. Animals were sacrificed on day 7, and the sciatic nerve, spinal cord, and DRG were collected for further analysis. |
Dosage form | 10mg/kg/day for 7 days; i.p. |
Applications | WWL 70 significantly alleviated CCI-induced thermal hyperalgesia and mechanical allodynia, and reduced microglia activation, macrophage infiltration, and the production of nociceptive mediators in the ipsilateral lumbar spinal cord dorsal horn, DRG, and sciatic nerve. |
References: | |
| 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 | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2858 mL | 11.4288 mL | 22.8577 mL |
| 5 mM | 457.2 μL | 2.2858 mL | 4.5715 mL |
| 10 mM | 228.6 μL | 1.1429 mL | 2.2858 mL |
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
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