Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov 2009 Oct;8(10):794-805
Date
10/02/2009Pubmed ID
19794443Pubmed Central ID
PMC3021468DOI
10.1038/nrd2875Scopus ID
2-s2.0-70349636047 (requires institutional sign-in at Scopus site) 510 CitationsAbstract
The cardiovascular effects of epoxyeicosatrienoic acids (EETs) include vasodilation, antimigratory actions on vascular smooth muscle cells and anti-inflammatory actions. These endogenous lipid mediators are broken down into diols by soluble epoxide hydrolase (sEH), and so inhibiting this enzyme would be expected to enhance the beneficial cardiovascular properties of EETs. sEH inhibitors (sEHIs) that are based on 1,3-disubstituted urea have been rapidly developed, and have been shown to be antihypertensive and anti-inflammatory, and to protect the brain, heart and kidney from damage. Although challenges for the future exist - including improving the drug-like properties of sEHIs and finding better ways to target sEHIs to specific tissues - the recent initiation of the first clinical trials of sEHIs has highlighted the therapeutic potential of these agents.
Author List
Imig JD, Hammock BDMESH terms used to index this publication - Major topics in bold
AnimalsCardiovascular Agents
Cardiovascular Diseases
Drug Delivery Systems
Enzyme Inhibitors
Epoxide Hydrolases
Humans
Signal Transduction