FLAP inhibitors for the treatment of inflammatory diseases.

摘要: Leukotrienes are lipid inflammatory mediators that implicated in asthma, COPD, arthritis, cardiovascular disease and cancer. Leukotriene synthesis requires 5-lipoxygenase activating protein (FLAP), which acts as a scaffolding for the assembly of other enzymes involved leukotriene synthetic pathway occurring at nuclear envelope leukocytes. By blocking formation both B4 cysteinyl leukotrienes (ie, LTC4 , LTD4 LTE4), FLAP inhibitors act broad-spectrum leukotriene-modifier drugs may have wide range therapeutic applications. such MK-886, MK-0591 veliflapon (BAY-X-1005, DG-031) demonstrated promise clinical trials with patients diseases mid 1990 s, but, unlike 'lukast' class cysteinyl-leukotriene receptor antagonists, these compounds were not brought to market. The elucidation 3D structure has enabled novel compound development, several including 2190914 (AM-103) GSK-2190915 (both under development by GlaxoSmithKline plc) entered phase II treatment disease, asthma.