CHAPTER 3:Leukotriene A4 Hydrolase: Biology, Inhibitors and Clinical Applications

Leukotriene A4 hydrolase is a zinc-containing cytosolic enzyme with both hydrolase and aminopeptidase activity. LTA4H stereospecifically catalyzes the transformation of the unstable epoxide LTA4 to the potent pro-inflammatory mediator LTB4. Variations in the lta4h gene have been linked to susceptibility to multiple diseases including myocardial infarction, stroke and asthma. Pre-clinical animal models and human biomarker data have implicated LTB4 in inflammatory diseases. Several groups have now identified selective inhibitors of LTA4H, many of which were influenced by the disclosure of a protein crystal structure a decade ago. Clinical validation of LTA4H remains elusive despite the progression of inhibitors into pre-clinical and clinical development.