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