花生四烯酸代谢网络研究：从关键酶的单靶标抑制剂到多靶标抑制剂

Controlling arachidonic acid metabolic network: from single-to multi-target inhibitors of key enzymes

炎症引发的疾病是人类常见的免疫系统疾病,医药市场对抗炎药物的需求量极大。花生四烯酸代谢网络是产生炎症介质的主要网络,网络中的一些蛋白质已成为抗炎药物设计的重要靶标,但这些单靶标药物不能很好地控制网络的平衡,同时容易引起副作用。大多数炎症引发的疾病是由多级联炎症代谢共同影响的结果,为了更好地治疗这类由多个药靶参与调控的复杂疾病,发展针对花生四烯酸代谢网络的多靶标药物具有迫切性。本文综述花生四烯酸代谢网络的关键靶标(如磷脂酶A2、环氧合酶、5-脂氧合酶和白三烯A4水解酶等)的特异性抑制剂和多靶标抑制剂研究进展。

Inflammatory diseases are common medical conditions seen in disorders of human immune system. There is a great demand for anti-inflammatory drugs. There are major inflammatory mediators in arachidonic acid metabolic network. Several enzymes in this network have been used as key targets for the development of anti-inflammatory drugs. However, specific single-target inhibitors can not sufficiently control the network balance and may cause side effects at the same time. Most inflammation induced diseases come from the complicated coupling of inflammatory cascades involving multiple targets. In order to treat these complicated diseases, drugs that can intervene multi-targets at the same time attracted much attention. The goal of this review is mainly focused on the key enzymes in arachidonic acid metabolic network, such as phospholipase A2, cyclooxygenase, 5-lipoxygenase and eukotriene A4 hydrolase. Advance in single target and multi-targe inhibitors is summarized.