FLAP inhibitors for the treatment of inflammatory diseases
FLAP inhibitors for the treatment of inflammatory diseases
Leukotrienes are lipid inflammatory mediators that are implicated in asthma, COPD, arthritis, cardiovascular disease and cancer. Leukotriene synthesis requires 5-lipoxygenase activating protein (FLAP), which acts as a scaffolding protein for the assembly of other enzymes involved in the leukotriene synthetic pathway occurring at the nuclear envelope of leukocytes. By blocking the formation of both leukotriene B4 and the cysteinyl leukotrienes (ie, LTC4 , LTD4 and LTE4), FLAP inhibitors act as broad-spectrum leukotriene-modifier drugs that may have a wide range of therapeutic applications. FLAP inhibitors such as MK-886, MK-0591 and veliflapon (BAY-X-1005, DG-031) demonstrated promise in clinical trials with patients with inflammatory diseases in the mid 1990 s, but, unlike the 'lukast' class of cysteinyl-leukotriene receptor antagonists, these compounds were not brought to market. The elucidation of the 3D structure of FLAP has enabled novel compound development, and several FLAP inhibitors including 2190914 (AM-103) and GSK-2190915 (both under development by GlaxoSmithKline plc) have entered phase II trials for the treatment of inflammatory disease, including asthma.
1163-1172
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
November 2009
Sampson, A.P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Sampson, A.P.
(2009)
FLAP inhibitors for the treatment of inflammatory diseases.
Current Opinion in Investigational Drugs, 10 (11), .
(PMID:19876784)
Abstract
Leukotrienes are lipid inflammatory mediators that are implicated in asthma, COPD, arthritis, cardiovascular disease and cancer. Leukotriene synthesis requires 5-lipoxygenase activating protein (FLAP), which acts as a scaffolding protein for the assembly of other enzymes involved in the leukotriene synthetic pathway occurring at the nuclear envelope of leukocytes. By blocking the formation of both leukotriene B4 and the cysteinyl leukotrienes (ie, LTC4 , LTD4 and LTE4), FLAP inhibitors act as broad-spectrum leukotriene-modifier drugs that may have a wide range of therapeutic applications. FLAP inhibitors such as MK-886, MK-0591 and veliflapon (BAY-X-1005, DG-031) demonstrated promise in clinical trials with patients with inflammatory diseases in the mid 1990 s, but, unlike the 'lukast' class of cysteinyl-leukotriene receptor antagonists, these compounds were not brought to market. The elucidation of the 3D structure of FLAP has enabled novel compound development, and several FLAP inhibitors including 2190914 (AM-103) and GSK-2190915 (both under development by GlaxoSmithKline plc) have entered phase II trials for the treatment of inflammatory disease, including asthma.
Text
__soton.ac.uk_ude_PersonalFiles_Users_aps_mydocuments_Reviews_Curr Op Invest Drugs - FLAP Inhibitors_Revision_Sampson_FLAP_2009_0631_REVISED PDF FINAL COID 10_1163-72.pdf
- Version of Record
Restricted to Registered users only
Request a copy
More information
Published date: November 2009
Identifiers
Local EPrints ID: 73113
URI: http://eprints.soton.ac.uk/id/eprint/73113
ISSN: 1472-4472
PURE UUID: 8601f0d6-154b-4741-9ce4-0cc6cfea45aa
Catalogue record
Date deposited: 02 Mar 2010
Last modified: 14 Mar 2024 02:39
Export record
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
