5-lipoxygenase: A target for antiinflammatory drugs revisited

Arachidonate 5-lipoxygenase is the key enzyme in leukotriene biosynthesis a nd catalyzes the initial steps in the conversion of arachidonic acid to bio logically active leukotrienes. Leukotrienes are considered as potent potent mediators of inflammatory and allergic reactions which are locally release d by leukocytes and other 5-LO expressing cells and exert their effects via binding to specific membrane receptors and, as suggested recently, the nuc lear receptor PPAR alpha. Because of the proinflammatory profile of leukotrienes it was assumed that leukotriene biosynthesis inhibitors and leukotriene receptor antagonists ha ve a therapeutical potential in a variety of inflammatory diseases. Clinica l studies confirmed the therapeutic value of the antileukotriene therapy in asthma but the results with leukotriene biosynthesis inhibitors in psorias is, arthritis and inflammatory bowel disease were more or less disappointin g. This review summarizes the biochemistry of the 5-lipoxygenase pathway, t he pharmacology of FLAP and 5-lipoxygenase inhibitors and discusses possibl e criteria for the development of these drugs.