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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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URB754 has no effect on the hydrolysis or signaling capacity of 2-AG in the rat brain.

Previous studies indicate that in brain tissue the endocannabinoid 2-AG is inactivated by monoglyceride lipase (MGL)-catalyzed hydrolysis, and a recent report has indicated that MGL activity could be specifically inhibited by URB754 . In the present study, URB754 failed to inhibit 2-AG hydrolysis in rat brain preparations. In addition, brain cryosections were employed to assess whether URB754 could facilitate the detection of 2-AG-stimulated G protein activity. Nevertheless, whereas pretreatment with PMSF readily allowed detection of 2-AG-stimulated G protein activity, URB754 was ineffective. In contrast to previous claims, brain FAAH activity was also resistant to URB754. Thus, in our hands URB754 was not able to block the endocannabinoid-hydrolyzing enzymes and cannot serve as a lead structure for future development of MGL-specific inhibitors.[1]

References

  1. URB754 has no effect on the hydrolysis or signaling capacity of 2-AG in the rat brain. Saario, S.M., Palomäki, V., Lehtonen, M., Nevalainen, T., Järvinen, T., Laitinen, J.T. Chem. Biol. (2006) [Pubmed]
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