Cyclooxygenase: Past, present and future. A tribute to John R. Vane (1927-2004)

Study of the prostagiandins led directly to the elucidation of the mode of action of aspirin which inhibits their synthesis. John Vane elegantly demonstrated in 1971 that non-steroid anti-inflammatory drugs (NSAIDs) blocked cyclooxygenase (COX), the enzyme which makes prostaglandins. In 1991, Daniel Simmons described the gene which expresses a second cyclooxygenase, COX-2. This discovery explained the anti-inflammatory actions of NSAIDs, inhibition of COX-2, and their side actions, inhibition of COX-L Within 8 years selective COX-2 inhibitors became available for the treatment of inflammation without the disadvantage of gastric toxicity. Recently, a COX-1 variant protein, named COX-3, sensitive to inhibition with acetaminophen, was characterised, cloned and expressed. (c) 2005 Elsevier Ltd. All rights reserved.