Journal
CHEMISTRY & BIOLOGY
Volume 14, Issue 12, Pages 1357-1365Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2007.10.017
Keywords
-
Categories
Funding
- NIDA NIH HHS [R01 DA-012447, R01 DA012447-07, R01 DA012447] Funding Source: Medline
- NINDS NIH HHS [T32 NS007444, T32NS007444-7, T32 NS007444-07] Funding Source: Medline
Ask authors/readers for more resources
The N-aryl carbamate URB602 (biphenyl-3-ylcarbamic acid cyclohexyl ester) is an inhibitor of monoacylglycerol lipase (MGL), a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyi-sn-glycerol (2-AG). Here, we investigated the mechanism by which URB602 inhibits purified recombinant rat MGL by using a combination of biochemical and structure-activity relationship (SAR) approaches. We found that URB602 weakly inhibits recombinant MGL (IC50 = 223 +/- 63 mu M) through a rapid and noncompetitive mechanism. Dialysis experiments and SAR analyses suggest that URB602 acts through a partially reversible mechanism rather than by irreversible carbamoylation of MGL. Finally, URB602 (100 mu M) elevates 2-AG levels in hippocampal slice cultures without affecting levels of other endocannabinoid-related substances. Thus, URB602 may provide a useful tool by which to investigate the physiological roles of 2-AG and explore the potential interest of MGL as a therapeutic target.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available