|
KMID : 0370220120560010042
|
|
Yakhak Hoeji
2012 Volume.56 No. 1 p.42 ~ p.47
|
|
|
Development of Soluble Epoxide Hydrolase Inhibitor Screening Methods for Discovery of Drug Candidate in Cardiovascular Diseases
|
|
Lee Gwan-Ho
Kim Bong-Hee
Kim Sang-Kyum
|
|
|
Abstract
|
|
|
|
Soluble epoxide hydrolase (sEH) is a metabolic regulator of epoxyeicosatrienoic acids (EETs). EETs have many beneficial effects, vasodilation, anti-diabetes, anti-inflammation, cardiovascular protection, renal protection. Therefore, selective sEH inhibitors have a potential for treating these diseases. In the present study, screening methods for sEH inhibitors using PHOME ((3-phenyl-oxiranyl)-acetic acid cyano-(6-methoxynaphthalen-2-yl)-methyl ester) and 14-15-EET as substrates were established. To determine selectivity, microsomal epoxide hydrolase (mEH) inhibition assay was also developed using styrene oxide as a substrate of microsomal epoxide hydrolase. Our results obtained from 12-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]-dodecanoic acid (AUDA) used as a positive sEH inhibitor and valpromide used as a positive mEH inhibitor showed that these methods are useful for discovery of drug candidates.
|
|
|
KEYWORD
|
|
|
soluble epoxide hydrolase, 14, 15-epoxyeicosatrienoic acid, cardiovascular disease, soluble epoxide hydrolase inhibitor, microsomal epoxide hydrolase
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|