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金诺芬的潜在抗癌活性

[Potential Anticancer Activity of Auranofin].

作者信息

Momose Isao, Onodera Takefumi, Kawada Manabu

机构信息

Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation.

出版信息

Yakugaku Zasshi. 2021;141(3):315-321. doi: 10.1248/yakushi.20-00179-2.

Abstract

Gold compounds have been employed throughout history to treat various types of disease, from ancient times to the present day. In the year 1985, auranofin, a gold-containing compound, was approved by U.S. Food and Drug Administration (FDA) as a therapeutic agent to target rheumatoid arthritis that would facilitate easy oral drug administration as opposed to conventional intramuscular injection used in treatments. Furthermore, auranofin demonstrates promising results for the treatment of various diseases beyond rheumatoid arthritis, including cancer, neurodegenerative diseases, acquired immune deficiency syndrome, and bacterial and parasitic infections. Various potential novel applications for auranofin have been proposed for treating human diseases. Auranofin has previously been demonstrated to inhibit thioredoxin reductase (TrxR) involved within the thioredoxin (Trx) system that comprises one of the critical cellular redox systems within the body. TrxR comprises the sole known enzyme that catalyzes Trx reduction. With cancers in particular, TrxR inhibition facilitates an increase in cellular oxidative stress and suppresses tumor growth. In this review, we describe the potential of auranofin to serve as an anticancer agent and further drug repurposing to utilize this as a strategy for further appropriate drug developments.

摘要

从古至今,金化合物一直被用于治疗各种疾病。1985年,一种含金化合物——金诺芬,被美国食品药品监督管理局(FDA)批准作为治疗类风湿性关节炎的药物,与传统的肌肉注射治疗方式相比,它便于口服给药。此外,金诺芬在治疗类风湿性关节炎以外的各种疾病方面也显示出了有前景的效果,包括癌症、神经退行性疾病、获得性免疫缺陷综合征以及细菌和寄生虫感染。人们已经提出了金诺芬在治疗人类疾病方面的各种潜在新应用。金诺芬此前已被证明能抑制硫氧还蛋白还原酶(TrxR),该酶参与硫氧还蛋白(Trx)系统,而硫氧还蛋白系统是体内关键的细胞氧化还原系统之一。TrxR是唯一已知的催化Trx还原的酶。特别是对于癌症,抑制TrxR会促进细胞氧化应激增加并抑制肿瘤生长。在这篇综述中,我们描述了金诺芬作为抗癌药物的潜力,以及进一步将药物重新用于其他用途,以此作为进一步合理药物开发的策略。

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