Biological Activity
bay-x 1005 is a selective inhibitor of 5-lipoxygenase-activating protein [1].5-lipoxygenase-activating protein (flap) is an integral protein and plays an important role in the activation of 5-lipoxygenase (5-lox) and the synthesis of leukotrienes, which regulating immune responses.bay-x 1005 is a selective inhibitor of leukotriene synthesis. bay x 1005 binds to flap and inhibits 5-lox translocation from the cytosol to membranes [1]. bay-x1005 inhibited ltb4 synthesis with ic50 values of 0.22, 0.026 and 0.039 μm for isolated pmnl of human, rat and mouse respectively and inhibited ltc4 synthesis with ic50 value of 0.021 μm in mouse macrophages [2].in the arachidonate-induced mouse ear inflammation test, bay-x 1005 inhibited myeloperoxidase activity and edema formation with ed50 values of 7.9 and 48.7, respectively [2].also, bay-x 1005 (100 mg/kg) reduced platelet-activating factor-induced death of mice by 51% in a dose-dependent way. in animal models, bay-x 1005 inhibited the synthesis of ltb4 and ltc4, which reduced edema formation, the vascular phenomena of inflammation and leukocyte immigration [3].
References
[1]. hatzelmann a, fruchtmann r, mohrs kh, et al. mode of action of the leukotriene synthesis (flap) inhibitor bay x 1005: implications for biological regulation of 5-lipoxygenase. agents actions, 1994, 43(1-2): 64-68.
[2]. müller-peddinghaus r, fruchtmann r, ahr hj, et al. bay x1005, a new selective inhibitor of leukotriene synthesis: pharmacology and pharmacokinetics. j lipid mediat, 1993, 6(1-3): 245-248.
[3]. müller-peddinghaus r, kohlsdorfer c, theisen-popp p, et al. bay x1005, a new inhibitor of leukotriene synthesis: in vivo inflammation pharmacology and pharmacokinetics. j pharmacol exp ther, 1993, 267(1): 51-57.
