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Zileuton sodium (A 64077 sodium) is a potent and selective inhibitor of 5-lipoxygenase, exhibiting inflammatory activities. | [Biological Activity]
zileuton sodium is an inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes(ltb4, ltc4, ltd4 and lte4) formation with an ic50 value of 0.5μm [1].zileuton sodium has been reported to concentration-dependently inhibit the 5-lipoxygenase activity with an ic50 value of 0.5μm in rbl-1cell lysate. in addition, zileuton sodium has been found to be a potent inhibitor of ltb formation with an ic50 value of 0.6μm. furthermore, stimulated with a23187, zileuton sodium has shown a dose-dependent reduction in ltb4 and 5-hete generation in rat leukocyte with ic50 values of 0.38μm and 0.31μm, respectively. about 40-fold higher concentrations of zileuton sodium also reduced the production of pge2 with a ic50 of 16μm [1]. | [in vivo]
In Zileuton sodium (A 64077 sodium) (5 mg/kg, p.o.) treated I/R rat, the effect of Zileuton to decrease NF-κB expression does not change significantly in the presence of COX inhibitors, and the group reveals significantly lower level of NF-κB staining. Zileuton (5 mg/kg, p.o.) treatment given to I/R rats decreases apoptotic index significantly. Zileuton has no significant effect on increased serum TNF-α levels in I/R group[1].
Zileuton sodium (A 64077 sodium) (1200 mg/kg) inhibits the polyp formation in APCΔ468 colon and small intestine. Zileuton treatment inhibits the proliferation rates of non epithelial cells in polyps, and increases the apoptosis rates in polyps in rat. There is significant increase in the number of apoptotic cells in the Zileuton-treated cells both in small intestine and in the colon. The reduced proliferation rate may significantly contribute to the reduction of polyposis in both the small intestine and colon of Zileuton-fed APCΔ468 mice[3]. | [IC 50]
5-Lipoxygenase | [References]
[1] carter gw1, young pr, albert dh, bouska j, dyer r, bell rl, summers jb, brooks dw. 5-lipoxygenase inhibitory activity of zileuton. j pharmacol exp ther. 1991 mar; 256(3):929-37. |
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