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What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases.
What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases.
- Source :
-
Trends in pharmacological sciences [Trends Pharmacol Sci] 2008 Feb; Vol. 29 (2), pp. 72-8. Date of Electronic Publication: 2008 Jan 09. - Publication Year :
- 2008
-
Abstract
- Leukotrienes have physiological roles in innate immune responses and pathological roles in inflammatory diseases, such as asthma, allergic rhinitis and atherosclerosis. Anti-leukotriene therapy has proven benefits in the treatment of respiratory disease, either through the inhibition of leukotriene synthesis or the selective antagonism of leukotriene receptors. The first committed step in the synthesis of leukotrienes is the oxidation of arachidonic acid (AA) by 5-lipoxygenase (5-LO), and the integral membrane protein 5-lipoxygenase-activating protein (FLAP) is an essential partner of 5-LO for this process. FLAP was molecularly identified via a photoaffinity probe and an affinity gel based on MK-886, a selective leukotriene inhibitor that has no activity against broken-cell preparations of 5-LO. Several FLAP inhibitors showed efficacy in early clinical trials in asthma but were not developed commercially for unpublished reasons. Recently, the FLAP (ALOX5AP) gene has been linked to risk for myocardial infarction, stroke and restenosis, reigniting pharmaceutical interest in this target. In addition, the recent determination of the crystal structure of inhibitor-bound FLAP offers exciting potential for novel FLAP inhibitor design.
- Subjects :
- 5-Lipoxygenase-Activating Proteins
Animals
Asthma drug therapy
Asthma physiopathology
Cardiovascular Diseases drug therapy
Cardiovascular Diseases physiopathology
Carrier Proteins genetics
Carrier Proteins metabolism
Controlled Clinical Trials as Topic
Drug Evaluation, Preclinical
Humans
Leukotrienes biosynthesis
Membrane Proteins genetics
Membrane Proteins metabolism
Carrier Proteins antagonists & inhibitors
Drug Delivery Systems
Drug Design
Membrane Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0165-6147
- Volume :
- 29
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Trends in pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 18187210
- Full Text :
- https://doi.org/10.1016/j.tips.2007.11.006