K. Moreland - A three-step kinetic mechanism for selective inhibition of cyclo-oxygenase-2 by diarylheterocyclic inhibitors

Version 1

      Publication Details (including relevant citation   information):

      Biochemical Journal

      Vol. 357, No. Pt3, pg. 709-18 (2001)

      ISSN: 0264-6021 (Print)



      Cyclo-oxygenase (COX) enzymes are the targets for non-steroidal   anti-inflammatory drugs (NSAIDs). These drugs demonstrate a   variety of inhibitory mechanisms, which include simple   competitive, as well as slow binding and irreversible inhibition.   In general, most NSAIDs inhibit COX-1 and -2 by similar   mechanisms. A unique class of diarylheterocyclic inhibitors has   been developed that is highly selective for COX-2 by virtue of   distinct inhibitory mechanisms for each isoenzyme. Several of   these inhibitors, with varying selectivity, have been utilized to   probe the mechanisms of COX inhibition. Results from analysis of   both steady-state and time-dependent inhibition were compared. A   generalized mechanism for inhibition, consisting of three   sequential reversible steps, can account for the various types of   kinetic behaviour observed with these inhibitors.

      Address (URL): http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citati on&list_uids=11463341