Leukotriene Synthesis (FLAP) Inhibition: Biochemistry and Pharmacology of Bay X 1005

Leukotrienes have been recognized as mediators of inflammatory allergic diseases of the lung (22). Consequently, antileukotriene therapy appears to be nearly established as novel pharmacotherapy of allergic asthma (15, 31). Cysteinyl-leukotrienes (LTC4, LTD4, LTE4) appear to have considerable pathophysiological importance in allergie asthma, because functional lung parameters improve with antileukotriene therapy after LTD4 challenge, antigen provocation, cold air exposure, exercise-induced asthma, and even aspirin-induced asthma (22, 24, 46). Effective antileukotriene therapy comprises various LTD4 receptor antagonists (LTD4ra) and 5-lipoxygenase (5-LOX) inhibitors (15, 22). 5-LOX inhibitors can be differentiated into the direct 5-LOX inhibitors (LOI) and FLAP (Five Lipoxygenase Activating Protein) binding leukotriene synthesis inhibitors (LSI) (Figure 1).