小分子多肽类似物研究进展research progress of small - 药学学报.pdf

药学学报 Acta Pharmaceutica Sinica 20 15, 50 (8): 931 944 ·931 · 分子多肽类似物研究进展 佳, 孙德群* ( 山东大学 (威海) 海洋学院, 山东 威海264209) 摘要: 多肽类药物的研究是新药研发的重要方向, 然而许多天然大分子多肽代谢不稳定且生物利用度低, 在临床用 方面受到限制。近年来, 小分子活性多肽类似物因其具有分子量小、生物活性高以及结构易修饰等 特点, 开启了多肽类 物研发的新热点, 并有多个此类 物已上市或已进入临床研究阶段。本文详细介绍了美国 FDA 于2005～20 14 年批准上市的小分子多肽类似物的研究现状, 就其来源、合成方法、化学结构特点、上市时 间、适应证以及临床有效性和安全性等方面进行综述, 并展望了该领域今后的发展方向。 关键词: 小分子肽; 多肽类似物; 临床试验研究 中图分类号: R9 16; R963 文献标识码: A 文章编号: 0513-4870 (20 15) 08-0931-14 Research progress of small peptidomimetics * WANG Jia, SUN De-qun (Mar ine College, Shandong University, Weihai 264209, China ) Abstract : The study of peptide drugs has been an important direction in research and development of new drugs. However, lots of natural macromolecular peptides are limited in clinical use by their metabolic instability and low bioavailability. In recent years, the active small peptidomimetics open up a new hotspot of peptide drug development with the characteristics of low molecular weight, high bioactivity and structural modification. Many peptidomimetics are on the market or on the clinical study. This paper elaborated the small peptidomimetics approved by American Food and Drug Administration (FDA) from 2005 to 2014, and reviewed their researching status with source, synthetic method, chemical structure, marketing time, indication, clinical efficacy and safety. Research prospects in this field wer