O-7460
In humans, two forms of diacylglycerol lipase, DAGLA and DAGLB, generate the endocannabinoid 2-arachidonoyl glycerol (2-AG) by attacking DAG at the sn-1 position. O-7460 is a selective inhibitor of 2-AG biosynthesis via DAGL (IC50 = 690 nM). It demonstrates much weaker inhibition towards human monoacylglycerol lipase and rat brain fatty acid amide hydrolase (IC50s > 10 uM) and does not bind to CB1 or CB2 cannabinoid receptors (Kis > 10 uM).1 At 0-12 mg/kg, i.p. in mice, O-7460 was reported to dose-dependently inhibit high-fat diet intake and reduce body weight.
General
Type : Organophosphate,Analogue of substrate,Lipase inhibitor,Triacylglycerol
Chemical_Nomenclature : 2-[(fluoromethylphosphinyl)oxy]-1-[(1-methylethoxy)methyl]ethyl ester, 9Z-octadecenoic acid
Canonical SMILES : CC(C)OCC(OC(CCCCCCC\/C=CCCCCCCCC)=O)COP(F)(C)=O
InChI : InChI=1S\/C25H48FO5P\/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-25(27)31-24(21-29-23(2)3)22-30-32(4,26)28\/h12-13,23-24H,5-11,14-22H2,1-4H3\/b13-12-
InChIKey : ZLEFMXNNQCABDB-SEYXRHQNSA-N
Other name(s) :
MW : 478.62
Formula : C25H48FO5P
CAS_number : 1572051-31-0
PubChem : 132285144
UniChem : ZLEFMXNNQCABDB-SEYXRHQNSA-N
IUPHAR :
Wikipedia :
Target
References (1)
| Title : A novel fluorophosphonate inhibitor of the biosynthesis of the endocannabinoid 2-arachidonoylglycerol with potential anti-obesity effects - Bisogno_2013_Br.J.Pharmacol_169_784 |
| Author(s) : Bisogno T , Mahadevan A , Coccurello R , Chang JW , Allara M , Chen Y , Giacovazzo G , Lichtman A , Cravatt BF , Moles A , Di Marzo V |
| Ref : British Journal of Pharmacology , 169 :784 , 2013 |
| Abstract : Bisogno_2013_Br.J.Pharmacol_169_784 |
| ESTHER : Bisogno_2013_Br.J.Pharmacol_169_784 |
| PubMedSearch : Bisogno_2013_Br.J.Pharmacol_169_784 |
| PubMedID: 23072382 |
| Gene_locus related to this paper: human-DAGLA , human-DAGLB |