URB754

URB754 is a potent and noncompetitive inhibitor of monoacylglycerol lipase (MAGL), exhibiting an IC₅₀ value of 200 nM for the recombinant rat brain enzyme.¹ However, it does not inhibit human recombinant, rat brain, or mouse brain MAGL at concentrations up to 100 µM.^2,3 There is evidence that the MAGL inhibitory activity of URB754 may be attributed to the impurity bis(methylthio)mercurane (IC₅₀ = 11.9 nM for rat recombinant MAGL) that is found in commercial preparations.⁴ URB754 inhibits rat brain fatty acyl amide hydrolase (FAAH) with an IC₅₀ value of 32 µM and binds weakly to the rat central cannabinoid (CB₁) receptor with an IC₅₀ value of 3.8 µM.¹ It does not inhibit COX-1 or COX-2 at concentrations up to 100 µM.¹ Inhibition of MAGL hydrolysis of 2-arachidonoyl glycerol (2-AG) is associated with enhanced stress-induced analgesia and may represent a novel drug target in pain and stress management.⁵

WARNING This product is not for human or veterinary use.

1. Makara, J.K., Mor, M., Fegley, D., et al. Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus. Nat. Neurosci. 8(9), 1139-1141 (2005).

2. Saario, S.M., Palomäki, V., Lehtonen, M., et al. URB754 has no effect on the hydrolysis or signaling capacity of 2-AG in the rat brain. Chem. Biol. 13(8), 811-814 (2006).

3. Vandevoorde, S., Jonsson, K.O., Labar, G., et al. Lack of selectivity of URB602 for 2-oleoylglycerol compared to anandamide hydrolysis in vitro. Br. J. Pharmacol. 150(2), 186-191 (2007).

4. Tarzia, G., Antonietti, F., Duranti, A., et al. Identification of a bioactive impurity in a commercial sample of 6-methyl-2-p-tolylaminobenzo[d][1,3]oxazin-4-one (URB754). Ann. Chim. 97(9), 887-894 (2007).

5. Hohmann, A.G., Suplita, R.L., Bolton, N.M., et al. An endocannabinoid mechanism for stress-induced analgesia. Nature 435(7045), 1108-1112 (2005).