Identification of a bioactive impurity in a commercial sample of 6-methyl-2-p-tolylaminobenzo[d][1,3]oxazin-4-one (URB754)

  • Ann Chim. 2007 Sep;97(9):887-94. doi: 10.1002/adic.200790073.
Giorgio Tarzia  1 ,  Francesca Antonietti ,  Andrea Duranti ,  Andrea Tontini ,  Marco Mor ,  Silvia Rivara ,  Pietro Traldi ,  Giuseppe Astarita ,  Alvin King ,  Jason R Clapper ,  Daniele Piomelli
Affiliations
  • 1. Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino, Italy. [email protected]
PMID: 17970304 DOI: 10.1002/adic.200790073
Abstract

The compound URB754 was recently identified as a potent inhibitor of the endocannabinoid-deactivating enzyme monoacylglycerol Lipase (MGL) by screening of a commercial chemical library. Based on HPLC/MS, NMR and EI/MS analyses, the present paper shows that 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. Although this organomercurial compound is highly potent at inhibiting MGL (IC50 = 11.9 +/- 1.1 nM), its biological use is prohibited by its toxicity and target promiscuity.

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