药学学报, 2021, 56(2): 341-351
引用本文:
王磊, 尤启冬. 2020年首创性小分子药物研究实例浅析[J]. 药学学报, 2021, 56(2): 341-351.
WANG Lei, YOU Qi-dong. First-in-class small molecule drugs in 2020[J]. Acta Pharmaceutica Sinica, 2021, 56(2): 341-351.

2020年首创性小分子药物研究实例浅析
王磊1,2, 尤启冬1,2
1. 中国药科大学, 江苏省药物分子设计与成药性优化重点实验室, 江苏 南京 210009;
2. 中国药科大学药学院药物化学系, 江苏 南京 210009
摘要:
随着我国对创新药物研发的重视与投入,首创性(first-in-class)药物的研发逐渐成为各大药企和科研机构争相追求的目标。首创性药物的研制需要深厚的基础研究积累、大量的资金投入和创新的研究方法,往往是新药研究中的风向标。2020年,美国食品药品监督管理局(FDA)共批准上市了53个全新药物,小分子药物依旧以38项获批占据着研究的主流。其中包括多个首创性的小分子药物,例如首个通过靶向表观遗传靶标EZH2治疗肉瘤的药物他泽司他(tazemetostat)、首个通过新型附着机制起效的HIV-1药物磷坦姆沙韦(fostemsavir)、首个通过抑制异戊二烯化治疗早衰症的药物氯那法尼(lonafarnib)和首个通过激动黑皮质素4受体(MC4R)治疗罕见肥胖症的药物司美诺肽(setmelanotide)等。以上首创性药物的研究过程具有很强的代表性,其研究思路也各具特点,本文通过浅析其中3例首创性药物的研发背景、研发过程和治疗应用,以期为更多的首创性药物研究提供借鉴。
关键词:    首创性药物      新药研发      小分子药物     
First-in-class small molecule drugs in 2020
WANG Lei1,2, YOU Qi-dong1,2
1. Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;
2. Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
Abstract:
With the development of the research on innovative drugs in our country, first-in-class drugs are becoming a main goal for both pharmaceutical companies and scientific institutions. Discovery of first-in-class drugs require amounts of basic research, a massive investment and novel methods, acting as a beacon for the new drug development. In 2020, FDA totally approved 53 novel drugs with 38 small molecules, which still accounting for a major component. Among them, many first-in-class drugs are important including a first EZH2 inhibitor (tazemetostat) for the treatment of epithelioid sarcoma, a first attachment inhibitor (fostemsavir) with novel mechanism for the treatment of HIV, a first farnesyltransferase inhibitor (lonafarnib) for the treatment of Hutchinson-Gilford progeria syndrome (HGPS) and a first MC4 receptor agonist for the treatment of rare genetic diseases of obesity, etc. The research procedures of the above drugs are representative with new ideas. In this review, we outline 3 of the first-in-class drugs to discuss the research background, discovery and development process as well as the therapeutic potentials to provide methods and ideas for the further drug development.
Key words:    first-in-class    drug discovery    small molecule drug   
收稿日期: 2021-01-18
DOI: 10.16438/j.0513-4870.2021-0063
通讯作者: 尤启冬,Tel:86-25-83271351,E-mail:youqd@cpu.edu.cn
Email: youqd@cpu.edu.cn
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