BW-B 70C

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Background

BW-B 70C is a potent and selective inhibitor of 5-lipoxygenase [1].
5-lipoxygenase is an enzyme that transforms essential fatty acids (EFAs) into leukotrienes and is activated by 5-lipoxygenase activating protein (FLAP).
BW-B 70C is a potent and selective 5-lipoxygenase inhibitor. BW-B 70C had high potency and long duration in vivo and was considered as potential anti-asthma drug [1]. In sensitised guinea-pigs, BW B70C (2-50 mg/kg) inhibited bronchoconstriction induced by allergen in a dose-dependent way, which was consistent with the inhibitory activity of BW B70C against 5-lipoxygenase. Also, BW B70C (20 mg/kg) inhibited eosinophil infiltration by 67% [2]. In guinea-pigs, The 5-lipoxygenase inhibitor, BW B70C (30 mg/kg) inhibited leucocyte migration to the airways lumen, leukotriene C4 synthesis by alveolar macrophages and albumin microvascular leakage induced by endotoxin. However, BW B70C didn’t affect vascular leucocyte margination and the blood levels of secreted phospholipase A2 and TNF-α [3]. In a focal cerebral ischemia rat model, BW-B 70C improved neurological deficit scores and decreased infarctions. Also, BW-B 70C reduced 5-lipoxygenase (5-LOX) and inhibited inducible nitric oxide synthase (iNOS) expression through down-regulation of NF-κB [4].

[1]. Payne AN, Jackson WP, Salmon JA, et al. Hydroxamic acids and hydroxyureas as novel, selective 5-lipoxygenase inhibitors for possible use in asthma. Agents Actions Suppl, 1991, 34: 189-199.
[2]. Yeadon M, Dougan FL, Petrovic A, et al. Effect of BW B70C, a novel inhibitor of arachidonic acid 5-lipoxygenase, on allergen-induced bronchoconstriction and late-phase lung eosinophil accumulation in sensitised guinea-pigs. Agents Actions, 1993, 38(1-2): 8-18.
[3]. Bureau MF, De Castro CM, Cortese C, et al. 5-Lipoxygenase and endotoxin-induced microvascular albumin exchanges and leucocyte recruitment in guinea-pig lungs. Eur J Pharmacol, 1997, 324(1): 89-98.
[4]. Jatana M, Giri S, Ansari MA, et al. Inhibition of NF-kappaB activation by 5-lipoxygenase inhibitors protects brain against injury in a rat model of focal cerebral ischemia. J Neuroinflammation, 2006, 3: 12.