Reference

5-lipoxygenase: regulation and pharmacology

5-lipoxygenase: regulation and pharmacology. Werz, Oliver (Institute of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt D-60439, Germany). Medicinal Chemistry Reviews--Online, 1(2), 201-223 (English) 2004 Bentham Science Publishers Ltd. URL: http://www.ingentaconnect.com/content/ben/mcro/2004/00000001/000 00002. CODEN: MCREC9. ISSN: 1567-2034. DOCUMENT TYPE: Journal; General Review; (online computer file) CA Section: 1 (Pharmacology) A review. 5-Lipoxygenase (5-LO) plays an essential role in the biosynthesis of leukotrienes (LTs), proinflammatory mediators, which are mainly released from myeloid cells. Whereas LTB4 is a potent chemotactic and chemokinetic agent for leukocytes, the cysteinyl (cys) LTs C4, D4 and E4 cause vascular permeability and smooth muscle contraction. In view of these properties, LT synthesis inhibitors have been hypothesised to possess therapeutic potential for the treatment of asthma, allergic disorders and other inflammatory diseases. The expression of 5-LO in mammals is tightly regulated. Enzymic activity in vitro can be modulated by calcium, ATP, phosphatidylcholine and lipid hydroperoxide; nevertheless activation of cellular 5-LO in response to external stimuli is rather incompletely understood. Intensive research revealed that on cell stimulation, 5-LO redistributes to the nuclear membrane where it colocalises with 5-lipoxygenase-activating protein and cytosolic phospholipase A2. Accumulating data suggest that phosphorylation of 5-LO by p38 MAPK-regulated MAPKAP-kinases and extracellular signal-regulated kinases 1/2 regulates cellular 5-LO activity and influences redistribution of the enzyme in the cell. In addn., the cellular redox tone regulates 5-LO product formation, and 5-LO reactions may be influenced by cellular proteins phys. interacting with 5-LO. This review highlights the determinants of cellular 5-LO activity and summarizes the mol.In this experiment, several chemicals are used like 111406-87-2 and 7440-70-2 pharmacol. of 5-LO. .

Pharmacokinetics, safety, and ability to diminish leukotriene synthesis by zileuton, an inhibitor of 5-lipoxygenase

Pharmacokinetics, safety, and ability to diminish leukotriene synthesis by zileuton, an inhibitor of 5-lipoxygenase. Rubin, P.; Dube, L.Several substances are used for example 111406-87-2 which is its cas registry number.; Braeckman, R.; Swanson, L.; Hansen, R.; Albert, D.; Carter, G. (Abbott Lab., Abbott Park, IL 60064-3500, USA). Agents Actions Suppl., 35(Prog. Inflammation Res. Ther.), 103-16 (English) 1991. CODEN: AASUDJ. ISSN: 0379-0363. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Zileuton (I) is a potent and specific inhibitor of 5-lipoxygenase, the first dedicated enzyme in the metab. of arachidonic acid to the leukotrienes. The leukotrienes have been implicated in numerous pathol. conditions. I was given to normal human volunteers in single doses of 200-800 mg. Results of these studies indicated that I was well absorbed orally with an elimination half-life of approx. 2.5 h. Leukotriene B4 prodn. by ex vivo calcium ionophone stimulated whole blood was inhibited by up to 80% of baseline and correlated with plasma concns. I did not significantly inhibit cyclooxygenase as demonstrated by thromboxane B2 levels. There were no safety concerns that would preclude development. .