可溶性环氧化物水解酶作为心血管疾病的治疗靶点。
Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases.
作者信息
Imig John D, Hammock Bruce D
机构信息
Department of Pharmacology and Toxicology, Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
出版信息
Nat Rev Drug Discov. 2009 Oct;8(10):794-805. doi: 10.1038/nrd2875.
Abstract
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.
摘要
环氧二十碳三烯酸（EETs）的心血管效应包括血管舒张、对血管平滑肌细胞的抗迁移作用以及抗炎作用。这些内源性脂质介质可被可溶性环氧化物水解酶（sEH）分解为二醇，因此抑制该酶有望增强EETs的有益心血管特性。基于1,3 - 二取代脲的sEH抑制剂（sEHIs）已得到快速研发，并已显示出具有降压、抗炎作用，以及保护脑、心脏和肾脏免受损伤的作用。尽管未来仍存在挑战——包括改善sEHIs的类药性质以及找到将sEHIs靶向特定组织的更好方法——但sEHIs首次临床试验的近期启动凸显了这些药物的治疗潜力。
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