Disease relevance of Bwa 4C

• 6. Yeast-induced pyrexia in rats was reduced by both BW A4C (ED50 = 32 mg kg-1) and BW A797C (ED50 = 23 mg kg-1) [1].
• 5. BW A4C and BW A797C had little or no effect on carrageenin-induced hyperalgesia in rats or phenyl-benzoquinone-induced writhing in mice [1].
• BW A4C, a selective 5-lipoxygenase inhibitor, however, caused a highly significant inhibition in pleural effusion and a slight but significant decrease in LW/BW ratio [2].
• BW 755C (25 mg/kg) and the more selective lipoxygenase inhibitor BW A4C (20 micrograms/cavity) suppressed the pleural eosinophilia induced by bradykinin (50 micrograms/cavity), whereas the platelet-activating factor (PAF)-acether antagonist BN 52021 was inactive [3].
• 3. BW A4C (1 and 0.3 microM) did not prevent the onset of ventricular fibrillation and ventricular tachycardia despite a slight delay in the occurrence of ventricular fibrillation and cardiac arrest at the 0.3 microM concentration [4].

High impact information on Bwa 4C

• Mast cell- and lymphocyte-induced eosinophil survival were completely reversed by SB 201146, SKF 104353, BW A4C, and MK 886 [5].
• Furthermore, the release-enhancing effect of McNeil A 343 (10 microM) on noradrenaline release was also not altered by the 5-lipoxygenase inhibitor, BW A4C [6].
• For comparison, the effects of a 5-lipoxygenase inhibitor, BW A4C (1 x 10(-9)-10(-5) M), and a corticosteroid, budesonide (1 x 10(-10)-10(-5) M) were also examined [7].
• Likewise, when BW A4C was administered to guinea pigs intravenously (3 mg/kg), we observed a rapid and marked (approximately 90%) reduction in whole blood LTB4 production which returned to control (pre-drug values) by 5 hr [8].
• Indomethacin (3 microM) and the 5-lipoxygenase inhibitor, BW A4C (1 microM) were without effect on basal or evoked [3H]NE release, suggesting that endogenously formed arachidonic acid metabolites have no significant modulatory role in this in vitro system [9].

Biological context of Bwa 4C

• 1. The chemically novel acetohydroxamic acids, BW A4C, BW A137C and BW A797C, are potent inhibitors of the synthesis of leukotriene B4 (LTB4) from arachidonic acid by human leucocyte homogenates: the concentrations required for 50% inhibition (IC50) were 0.1 microM, 0.8 microM and 0.5 microM respectively [10].
• The initial phase of increased vascular permeability in the peritoneal cavity and LTB4 production was dose dependently inhibited by the 5-LO inhibitors phenidone, BW A4C, A63162, and ICI 207 968 but not by dexamethasone or colchicine [11].

Anatomical context of Bwa 4C

• 7. The accumulation of leucocytes in sponge exudates was reduced dose-dependently by BW A4C (ED50 = 54 mg kg-1) and BW A797C (ED50 = 16.7 mg kg-1) [1].
• The effects of BW A4C, a selective arachidonate 5-lipoxygenase (5-LO) inhibitor, on the progression of myocardial tissue injury were examined in anaesthetised, open-chest beagle dogs subjected to 90-min occlusion of the left anterior descending coronary artery (LAD) followed by 120-min reperfusion [12].

Associations of Bwa 4C with other chemical compounds

• 3. BW A4C and BW A797C had little or no effect on prostaglandin E2 (PGE2) concentrations in inflammatory exudates (ED50s greater than 100 mg kg-1) [1].
• These stimulatory effects of IL-1 beta and IL-6 were blocked by cyclo-oxygenase inhibitors, indomethacin (28 microM) and ibuprofen (100 nM), but not by the lipoxygenase inhibitor, BW A4C (10 micrograms/ml), suggesting that prostaglandins are involved in this process.(ABSTRACT TRUNCATED AT 250 WORDS)[13]
• BW A4C (N-(3-phenoxycinnamyl)acetohydroxamic acid) was the most potent with an IC50 of 0.2 microM, followed by zileuton (3-10 microM) and linoleate-hydroxamic acid (0.02 mM) [14].
• Chemical modification of BW A4C has resulted in compounds, including the alpha-methyl analogues BW B218C and BW A360C and the hydroxyurea BW B70C, that retain high in vitro potency as selective 5-LO inhibitors and, compared to BW A4C, have a higher potency and longer duration of action in vivo [15].

Gene context of Bwa 4C

• 1. Two selective inhibitors of arachidonate 5-lipoxygenase, BW A4C and BW A797C, have been studied for their effects on acute inflammatory responses following oral administration to rats and mice [1].
• The IL-5-induced eosinophil migration was also blocked by BW A4C, another lipoxygenase inhibitor [16].

Analytical, diagnostic and therapeutic context of Bwa 4C

• Selective 5-lipoxygenase inhibitor BW A4C does not influence progression of tissue injury in a canine model of regional myocardial ischaemia and reperfusion [12].

References