M.-Q. Zhang* Pages 67 - 78 ( 12 )
Recent pathophysiological and biochemical data indicate that the hydroxyl leukotriene LTB4 plays an important role in many inflammatory diseases, such as asthma, inflammatory bowel diseases, psoriasis, arthritis, etc. Blockade of LTB4 biosynthesis and/or actions therefore provides a sensable approach for the development of anti-inflammatory therapeutics. The current biosynthesis inhibitors of LTB4, e.g. 5-lipoxygenase (5-LO) inhibitors or 5- lipoxygenase activating protein (FLAP) inhibitors, are all non-selective and they also block the synthesis of cysteinyl leukotrienes and lipoxins. This total blockade of 5-LO pathway of arachidonic acid metabolism poses concerns for potentially unwanted effects. Selective inhibition of leukotriene A4 (LTA4) hydrolase, the key rate-limiting enzyme for the biosynthesis of LTB4, would only limit the synthesis of LTB4 with the synthesis of cysteinyl leukotrienes and lipoxins intact, thus providing an alternative approach for the therapeutic intervention of LTB4. This review summaries the current knowledge on the pathological functions of LTB4 in inflammatory diseases, biochemistry of LTA4 hydrolase and selective inhibition of LTA4 hydrolase.