Auranofin: repurposing an old drug for a golden new age.
Auranofin: repurposing an old drug for a golden new age.
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DOI：
10.1007/s40268-015-0083-y
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发表时间：
2015-03
期刊：
影响因子：
3
通讯作者：
Thomson, Melanie J
中科院分区：
文献类型：
--
作者：
Roder, Christine;Thomson, Melanie J
药物发现、开发和注册是与高失败率相关的昂贵且耗时的过程[Pessetto等人（Mol Cancer Ther 12：1299-1309，），Woodcock和Woosley（Annu Rev Med 59：1-12，）]。药物“再利用”是为已批准的药物确定新的治疗目的，比新药发现更经济实惠和可实现[Pessetto et al.（Mol Cancer Ther 12：1299-1309，）]。金诺芬是一种被批准用于治疗类风湿性关节炎的药物，但正在研究其在许多其他疾病中的潜在治疗应用，包括癌症、神经退行性疾病、HIV/AIDS、寄生虫感染和细菌感染[Tejman-Yarden et al.（Antimicrob Agents Chemother 57：2029-2035，）]。金诺芬的主要作用机制是通过抑制还原/氧化（氧化还原）酶，这些酶对于维持细胞内活性氧水平至关重要。这些酶的抑制导致细胞氧化应激和内在凋亡[Pessetto等（Mol Cancer Ther 12：1299-1309，），Fan等（Cell Death Dis 5：e1191，），Fiskus等（Cancer Res 74：2520-2532，），Marzano等（Free Radic Biol Med 42：872-881，）]。已经被批准用于人类使用的药物如金诺芬[Tejman-Yarden et al.（Antimicrob Agents Chemother 57：2029-2035，）]可以相对快速地用于其他疾病的临床使用，并且成本是新药的一小部分。
Drug discovery, development and registration is an expensive and time-consuming process associated with a high failure rate [Pessetto et al. (Mol Cancer Ther 12:1299–1309,), Woodcock and Woosley (Annu Rev Med 59:1–12,)]. Drug ‘repurposing’ is the identification of new therapeutic purposes for already approved drugs and is more affordable and achievable than novel drug discovery [Pessetto et al. (Mol Cancer Ther 12:1299–1309,)]. Auranofin is a drug that is approved for the treatment of rheumatoid arthritis but is being investigated for potential therapeutic application in a number of other diseases including cancer, neurodegenerative disorders, HIV/AIDS, parasitic infections and bacterial infections [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029–2035,)]. The main mechanism of action of auranofin is through the inhibition of reduction/oxidation (redox) enzymes that are essential for maintaining intracellular levels of reactive oxygen species. Inhibition of these enzymes leads to cellular oxidative stress and intrinsic apoptosis [Pessetto et al. (Mol Cancer Ther 12:1299–1309,), Fan et al. (Cell Death Dis 5:e1191,), Fiskus et al. (Cancer Res 74:2520–2532,), Marzano et al. (Free Radic Biol Med 42:872–881,)]. Drugs such as auranofin that have already been approved for human use [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029–2035,)] can be brought into clinical use for other diseases relatively quickly and for a fraction of the cost of new drugs.