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Zileuton

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Chemical Structure| 111406-87-2 同义名 : 齐留通(Zileuton) ;A 64077;Abbott 64077;ZYFLO CR.;trade name ZYFLO;ZYFLO
CAS号 : 111406-87-2
货号 : A202709
分子式 : C11H12N2O2S
纯度 : 97%
分子量 : 236.29
MDL号 : MFCD00866097
存储条件：

粉末 Keep in dark place,Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(444.37 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • lipoxygenase
描述 Leukotrienes (LT) are metabolites of arachidonic acid (AA) formed from the 5-lipoxygenase (5-LOX) pathway. They exhibit a number of biological effects such as contraction of smooth muscles, especially bronchoconstriction, increased vascular permeability, and migration of leukocytes to areas of inflammation. Zileuton is a potent and selective inhibitor of 5-lipoxygenase with antiasthmatic properties[3]. In macrophages, zileuton overinterfered with arachidonic acid (AA) release to inhibit PG biosynthesis. In activated mouse peritoneal macrophages and macrophage J774, zileuton significantly reduces PGE2 and 6-ketone prostaglandin F1α (PGF1α) levels[4]. In anti-CD3-treated cells, IL-2 decreased in zileuton-treated and untreated cells with increasing incubation time. Zileuton likely reduced IL-2 levels by inhibiting 5-lipoxygenase[3]. Zileuton treatement on rats with TNB colitis, however, showed a significant reduction in the macroscopic damage score after four weeks of treatment compared with 5-ASA and placebo groups. The intracolonic administration of 50 mg/kg of zileuton after colitis induction decreased the local peak release of LTB4 by 90%[5]. In zileuton (5 mg/kg, p.o.) treated ischemia/reperfusion (I/R) rat, the effect of zileuton to decrease NF-κB expression did not change significantly in the presence of COX inhibitors, and the group revealed significantly lower level of NF-κB staining. Zileuton (5 mg/kg, p.o.) treatment given to I/R rats decreased apoptotic index significantly. In 5-LOX gene knockout mice, administration of zileuton before I/R significantly reduced the degree of renal dysfunction (urea, creatinine) and injury (AST, histology). In addition, zileuton reduced the expression of ICAM-1 and the associated polymorphonuclear leukocyte infiltration caused by I/R of the mouse kidney[6]. Although zileuton inhibited LTB4 production in the peritonitis model more effectively than the LTA4H inhibitor, the influx of neutrophils into the peritoneum after 1 and 2h was significantly higher in zileuton- versus JNJ-26993135-treated animals[7].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00595114 - Completed - United States, Massachusetts ... 展开 >> Brigham and Women's Hospital Boston, Massachusetts, United States, 02115 收起 <<
NCT00595114 - Completed - -
NCT01125748 - Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.23mL

0.85mL

0.42mL

21.16mL

4.23mL

2.12mL

42.32mL

8.46mL

4.23mL
参考文献

[1]Rossi A, Pergola C, et al. The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages. Br J Pharmacol. 2010 Oct;161(3):555-70.

[2]Bertran X, Mane J, et al. Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor, accelerates healing in a rat model of chronic colitis. Gut. 1996 Jun;38(6):899-904.

[3]Abueid L, Uslu Ü, Cumbul A, Velioğlu Öğünç A, Ercan F, Alican İ. Inhibition of 5-lipoxygenase by zileuton in a rat model of myocardial infarction. Anatol J Cardiol. 2017 Apr;17(4):269-275. doi: 10.14744/AnatolJCardiol.2016.7248. Epub 2016 Nov 10. PMID: 27849187; PMCID: PMC5469106.

[4]Rossi A, Pergola C, Koeberle A, Hoffmann M, Dehm F, Bramanti P, Cuzzocrea S, Werz O, Sautebin L. The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages. Br J Pharmacol. 2010 Oct;161(3):555-70. doi: 10.1111/j.1476-5381.2010.00930.x. PMID: 20880396; PMCID: PMC2990155.

[5]Bertrán X, Mañé J, Fernández-Bañares F, Castellá E, Bartolí R, Ojanguren I, Esteve M, Gassull MA. Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor, accelerates healing in a rat model of chronic colitis. Gut. 1996 Jun;38(6):899-904. doi: 10.1136/gut.38.6.899. PMID: 8984030; PMCID: PMC1383199.

[6]Patel NS, Cuzzocrea S, Chatterjee PK, Di Paola R, Sautebin L, Britti D, Thiemermann C. Reduction of renal ischemia-reperfusion injury in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton. Mol Pharmacol. 2004 Aug;66(2):220-7. doi: 10.1124/mol.66.2.220. PMID: 15266012.

[7]Rao NL, Dunford PJ, Xue X, Jiang X, Lundeen KA, Coles F, Riley JP, Williams KN, Grice CA, Edwards JP, Karlsson L, Fourie AM. Anti-inflammatory activity of a potent, selective leukotriene A4 hydrolase inhibitor in comparison with the 5-lipoxygenase inhibitor zileuton. J Pharmacol Exp Ther. 2007 Jun;321(3):1154-60. doi: 10.1124/jpet.106.115436. Epub 2007 Mar 19. PMID: 17371808.