심혈관계 질환 치료제 후보물질 발굴을 위한 Soluble Epoxide Hydrolase 억제평가 방법 개발

• 영문명: Development of Soluble Epoxide Hydrolase Inhibitor Screening Methods for Discovery of Drug Candidate in Cardiovascular Diseases
• 발행기관: 대한약학회
• 저자명: 이관호(Gwan Ho Lee) 김봉희(Bong Hee Kim) 김상겸(Sang Kyum Kim)
• 간행물 정보: 『약학회지』제56권 제1호 (2012년), 42~47쪽, 전체 6쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2012.02.28

영문 초록

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.

키워드

soluble epoxide hydrolase 14,15-epoxyeicosatrienoic acid cardiovascular disease soluble epoxide hydrolase inhibitor microsomal epoxide hydrolase