URB754 explained

URB754 was originally reported by Piomelli et al. to be a potent, noncompetitive inhibitor of monoacylglycerol lipase (MGL).^[1] However, recent studies have shown that URB754 failed to inhibit recombinant MGL, and brain FAAH activity was also resistant to URB754.^[2] In a later study by Piomelli et al., the MGL-inhibitory activity attributed to URB754 is in fact due to a chemical impurity present in the commercial sample, identified as bis(methylthio)mercurane.^[3]

Notes and References

1. Makara JK, Mor M, Fegley D, Szabó SI, Kathuria S, Astarita G, Duranti A, Tontini A, Tarzia G, Rivara S, Freund TF, Piomelli D . Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus . Nat. Neurosci. . 8 . 9 . 1139–41 . 2005 . 16116451 . 10.1038/nn1521. 52810445 .
2. Saario SM, Palomäki V, Lehtonen M, Nevalainen T, Järvinen T, Laitinen JT . URB754 has no effect on the hydrolysis or signaling capacity of 2-AG in the rat brain . Chem. Biol. . 13 . 8 . 811–4 . 2006 . 16931330 . 10.1016/j.chembiol.2006.07.008. free .
3. 10.1002/adic.200790073. 17970304. Identification of a Bioactive Impurity in a Commercial Sample of 6-Methyl-2-p-Tolylaminobenzo[d][1,3]Oxazin-4-One (URB754)]. Annali di Chimica. 97. 9. 887–94. 2007. Tarzia. Giorgio. Antonietti. Francesca. Duranti. Andrea. Tontini. Andrea. Mor. Marco. Rivara. Silvia. Traldi. Pietro. Astarita. Giuseppe. King. Alvin. Clapper. Jason R.. Piomelli. Daniele.