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

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

Affiliation

  • 1 Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino, Italy. gat@uniurb.it
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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