Cyclooxygenase

Cyclooxygenases are iron-containing enzymes involved in the oxidation of arachidonic acid and other lipids. They carry out the starting step of the synthesis of prostanoids, which are important mediators of several physiological and pathological processes, among which are inflammation, blood clotting, and cancer. Two isoforms exist, which share a high degree of sequence identity (about 60%) but differ in gene expression, in the ability to oxidize lipids other than arachidonic acid, and in the link to terminal prostanoid synthases. COX is the target of the Non-Steroidal Antiinflammatory Drugs (NSAIDs), which are among the most widely used medicines in the world. These drugs belong to different chemical classes and are endowed with a different isoform selectivity; many of them have been discovered much before the elucidation of their biological target. A high number of X-ray structures of these enzymes in complex with inhibitors have helped to understand the important characteristics for drug-enzyme interaction and may also help the future design of new inhibitors. Since COX2 is the isoform induced by the inflammation process, great efforts to find selective COX2 inhibitor have been made between the last decade of 1900 and the beginning of 2000, resulting in several compounds being approved worldwide to control rheumatic diseases. Some of these were subsequently withdrawn from the market due to cardiovascular toxicity.