The hepoxilins and some analogues: a review of their biology

The hepoxilin pathway was discovered over two decades ago. Products in this pathway are derived through the 12S‐lipoxygenase/hepoxilin synthase enzyme system and contain intrinsic biological activity. This activity relates to the reorganization of calcium and potassium ions within the cell, and in i...

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Bibliographic Details
Published in:British journal of pharmacology 2009-10, Vol.158 (4), p.972-981
Main Author: Pace‐Asciak, Cecil R
Format: Article
Language:English
Subjects:
8,11,14-Eicosatrienoic Acid - analogs & derivatives
8,11,14-Eicosatrienoic Acid - metabolism
Animals
Arachidonate 12-Lipoxygenase
bioavailability
Biology
cancer
diabetes
efficacy
hepoxilin stable analogues
hepoxilins
Humans
inflammation
Intramolecular Oxidoreductases
novel therapeutics
Themed Section: Reviews
thrombosis
tolerance
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Summary:The hepoxilin pathway was discovered over two decades ago. Products in this pathway are derived through the 12S‐lipoxygenase/hepoxilin synthase enzyme system and contain intrinsic biological activity. This activity relates to the reorganization of calcium and potassium ions within the cell, and in inflammation and insulin secretion. Although the natural hepoxilins are chemically unstable, chemical analogues (PBTs) have been synthesized with chemical and biological stability. The PBTs antagonize the natural hepoxilins. The PBTs showed bioavailability, excellent tolerance and stability in vivo. In proof of principle studies in vivo in animal models, the PBTs have shown actions as anti‐inflammatory agents, anti‐thrombotic agents, anti‐cancer agents and anti‐diabetic agents. These studies demonstrate the effectiveness of the base structure of the hepoxilin (and PBT) molecule and serve as an excellent framework for the design and preparation of second‐generation compounds with improved pharmaceutical properties as therapeutics for the above‐mentioned diseases. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.2009.00168.x