5-Lipoxygenase inhibitors: a review of recent developments and patents

IMPORTANCE TO THE FIELD: Leukotrienes (LTs) are pivotal lipid mediators of inflammation and allergy and results from recent studies also suggest roles of LTs in cardiovascular diseases, cancer and osteoporosis. 5-Lipoxygenase (5-LO) catalyzes the first step in the biosynthesis of LTs from arachidonic acid, and based on the multiple potent pathophysiological actions of LTs, the pharmacological intervention with 5-LO is a challenge in the development of therapeutics. AREAS COVERED IN THIS REVIEW: We first summarize the biochemical regulation of 5-LO and the general pharmacological concepts in 5-LO inhibition by currently available compounds, and subsequently we report recent developments deduced from recent scientific publications and patents. WHAT THE READER WILL GAIN: A comprehensive overview about the different molecular pharmacological strategies to inhibit 5-LO and the most successful previous 5-LO inhibitors. The review also gives insights into novel concepts, for example, dual prostaglandin/LT synthesis inhibition and reveals novel compounds patented or developed within the past 5 years. TAKE HOME MESSAGE: Despite the increasing therapeutic indications of anti-LT therapy, the progress in the development of novel 5-LO inhibitors is moderate. However, novel molecular concepts in the intervention with LT biosynthesis seem promising.