Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor.

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Favia AD, Habrant D, Scarpelli R, Migliore M, Albani C, Bertozzi SM, Dionisi M, Tarozzo G, Piomelli D, Cavalli A, De Vivo M

Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor.

J Med Chem. 2012 Oct 25;55(20):8807-26. doi: 10.1021/jm3011146. Epub 2012 Oct 8.

PubMed ID
23043222 [ View in PubMed
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Abstract

Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the nonsteroidal anti-inflammatory drug carprofen as a multitarget-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2, and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several derivatives of carprofen, sharing this multitarget activity. This may result in improved analgesic efficacy and reduced side effects (Naidu et al. J. Pharmacol. Exp. Ther.2009, 329, 48-56; Fowler, C. J.; et al. J. Enzyme Inhib. Med. Chem.2012, in press; Sasso et al. Pharmacol. Res.2012, 65, 553). The new compounds are among the most potent multitarget FAAH/COX inhibitors reported so far in the literature and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CarprofenProstaglandin G/H synthase 2IC 50 (nM)>100000N/AN/ADetails
CarprofenProstaglandin G/H synthase 2IC 50 (nM)5300N/AN/ADetails
CarprofenProstaglandin G/H synthase 2IC 50 (nM)3900N/AN/ADetails
IbuprofenProstaglandin G/H synthase 2IC 50 (nM)36000N/AN/ADetails