Drugs that Target Lipoxygenases and Leukotrienes as Emerging Therapies for Asthma and Cancer

Candace   D.   Poff; Michael      Balazy

Abstract

Considerable amount of work has been done in the area of enzymatic and nonenzymatic oxidation of arachidonic acid. This effort resulted in understanding of the functions of lipid mediators - eicosanoids in various aspects of health and disease. A mechanism by which aspirin exerts therapeutic effects puzzled pharmacologists for a long time until John Vane, in 1971, discovered that aspirin and its congeners block formation of prostaglandins, a class of lipids that originate from oxidation of arachidonic acid by cyclooxygenase. Since that discovery the pharmacology of eicosanoids has substantially progressed, which resulted in new drugs available in clinics. In addition to many new inhibitors of cyclooxygenase, two isoforms of which are known, much effort has been given to find inhibitors of synthesis and function of leukotrienes, a class of lipids that are derived from 5-lipoxygenase. These lipids are generated in asthma and their uncontrolled biosynthesis aggravates the symptoms of asthma. A new class of drugs called lukasts, inhibitors of 5-LOX products, has been developed and entered clinics as the first new therapy to treat asthma in nearly 20 years. New discoveries in the field of lipoxygenase show great opportunities for drug development for cancer prevention and treatment as it has been established that lipoxygenases and their products are required for cancer growth. Intense research in this field is likely to produce new drugs in the near future.

Keywords: asthma, cance, lipoxygenases, leukotrienes

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