title: Identification of a bioactive impurity in a commercial sample of 6-methyl-2-p-tolylaminobenzo[d][1,3]oxazin-4-one (URB754).
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.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino, Italy. gat@uniurb.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tarzia
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonietti
authors.forename: Andrea
authors.initials: A
authors.lastname: Duranti
authors.forename: Andrea
authors.initials: A
authors.lastname: Tontini
authors.forename: Marco
authors.initials: M
authors.lastname: Mor
authors.forename: Silvia
authors.initials: S
authors.lastname: Rivara
authors.forename: Pietro
authors.initials: P
authors.lastname: Traldi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
authors.forename: Alvin
authors.initials: A
authors.lastname: King
authors.forename: Jason R
authors.initials: JR
authors.lastname: Clapper
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
mesh_terms: D000814:Aniline Compounds / Q000032:analysis*; D048588:Benzoxazines / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000814:Aniline Compounds; D048588:Benzoxazines; C514879:URB 754