脂蛋白相关磷脂酶A2抑制剂Darapladib的药效学研究进展

马全鑫, 陈民利*, 王逸平

中国药学杂志 ›› 2015, Vol. 50 ›› Issue (4) : 317-322.

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中国药学杂志
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中国药学杂志 ›› 2015, Vol. 50 ›› Issue (4) : 317-322. DOI: 10.11669/cpj.2015.04.012
综述

脂蛋白相关磷脂酶A2抑制剂Darapladib的药效学研究进展

  • 马全鑫1, 陈民利1*, 王逸平2
作者信息 +

Pharmacodynamics Recent Advances of a Lipoprotein-associated Phospholipase A2 Specific Inhibitor Darapladib

  • MA Quan-xin1,CHEN Min-li1*,WANG Yi-ping2
Author information +
文章历史 +

摘要

脂蛋白相关磷脂酶A2 (lipoprotein- associated Phospholipase A2,Lp- PLA2)是磷脂水解酶超家族中的一员,能水解低密度脂蛋白中的氧化修饰磷脂,产生溶血卵磷脂和氧化性游离脂肪酸两种促炎介质。最近研究发现Lp- PLA2能够介导炎症反应以及促进动脉粥样硬化(atherosclerosis , AS)的形成,现已成为一个新炎性反应标志物和心血管事件的独立风险预示因子。针对这一动脉粥样硬化过程中的关键酶设计的抑制剂很多。其中Darapladib是目前最接近上市的一种Lp- PLA2特异性抑制剂,目前其Ⅲ期临床试验已完成。Darapladib作为一种新兴的抗AS分子靶点药物,受到人们广泛的关注。已有多项研究表明它能降低Lp- PLA2的活性,减轻炎症反应,从而控制AS的发展与恶化。本文综述了Lp- PLA2及其抑制剂Darapladib在AS中的作用机制以及近年来 Darapladib的药效学研究进展。

Abstract

Lipoprotein- associated phospholipase A2 (Lp- PLA2) is a member of phospholipases superfamily which can hydrolyze oxidative phospholipid in low density lipoprotein (LDL), and produce two proinflammatory mediators including lysophosphatidylcholine (lysoPC) and oxidized free fatty acid. Thus, Lp- PLA2 is believed to mediate the inflammatory processes that lead to atherogenesis. Recent studies indicated that Lp- PLA2 acts as a new marker in the inflammatory process and is an independent predictor of the cardiovascular diseases. Many Lp- PLA2- targeted inhibitors have been designed to deal with the key enzyme involving in atherosclerosis. Darapladib is the specific inhibitor which is closest to the market among the rest and is drawn wide attention as an emerging therapy for atherosclerosis, and the clinical phase Ⅲ trials have been completed. Numerous experiments have confirmed that Darapladib could decrease the activity of Lp- PLA2, reduce inflammatory reaction and disrupt the development of atherosclerosis. In this paper, the authors summarized the mechanism of Lp- PLA2 and Darapladib in atherosclerosis, and the recent advances on the pharmacodynamics of Darapladib in recent years.

关键词

动脉粥样硬化 / 脂蛋白相关磷脂酶A2 / Darapladib

Key words

atherosclerosis / Lp-PLA2 / Darapladib

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马全鑫, 陈民利*, 王逸平. 脂蛋白相关磷脂酶A2抑制剂Darapladib的药效学研究进展[J]. 中国药学杂志, 2015, 50(4): 317-322 https://doi.org/10.11669/cpj.2015.04.012
MA Quan-xin,CHEN Min-li*,WANG Yi-ping. Pharmacodynamics Recent Advances of a Lipoprotein-associated Phospholipase A2 Specific Inhibitor Darapladib[J]. Chinese Pharmaceutical Journal, 2015, 50(4): 317-322 https://doi.org/10.11669/cpj.2015.04.012

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基金

国家科技重大专项子课题(2012zx09103101-008);“浙江省卫生高层次创新人才培养工程项目”资助

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