Proteases as therapeutics.
Proteases as therapeutics.
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DOI：
10.1042/bj20100965
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Madison EL
中科院分区：
文献类型：
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作者：
Craik CS;Page MJ;Madison EL
蛋白酶是一类不断扩大的药物，具有很大的前景。美国食品和药物管理局（FDA）已经批准了12种蛋白酶疗法，许多下一代或全新的蛋白酶正在临床开发中。尽管它们是抑制剂的公认靶点，蛋白酶本身通常不被认为是一种药物类别，尽管在过去的几十年里它们在临床中的应用；最初作为血浆组分，后来作为纯化产物。虽然蛋白酶的主要用途是治疗心血管疾病，但它们也在败血症、消化系统疾病、炎症、囊性纤维化、视网膜疾病、牛皮癣和其他疾病的治疗中成为有用的药物。在本综述中，我们概述了蛋白酶作为治疗药物的历史，概述了它们目前的临床应用，并描述了几种改善和扩大其临床应用的方法。毫无疑问，随着我们对蛋白酶生物学和相关分子机制的了解，我们利用蛋白质水解来治疗疾病的能力将会增加。合理设计蛋白酶的新技术，以及改进的递送选择，将极大地扩展这些酶的潜在应用。认识到蛋白酶实际上是一类安全有效的药物，将刺激对这些酶的其他治疗应用的研究。因此，蛋白酶作为一种独特的治疗类具有广阔的临床应用前景。
Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications.