Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, U.K.
Biochem Soc Trans. 2020 Feb 28;48(1):271-280. doi: 10.1042/BST20190694.
Fragment-based drug discovery (FBDD) has become a mainstream technology for the identification of chemical hit matter in drug discovery programs. To date, the food and drug administration has approved four drugs, and over forty compounds are in clinical studies that can trace their origins to a fragment-based screen. The challenges associated with implementing an FBDD approach are many and diverse, ranging from the library design to developing methods for identifying weak affinity compounds. In this article, we give an overview of current progress in fragment library design, fragment to lead optimisation and on the advancement in techniques used for screening. Finally, we will comment on the future opportunities and challenges in this field.
基于片段的药物发现（FBDD）已成为药物发现项目中鉴定化学命中物质的主流技术。迄今为止，美国食品和药物管理局已经批准了四种药物，超过四十种化合物正在进行临床研究，可以追溯到基于片段的筛选。实施 FBDD 方法所面临的挑战很多且多样，从文库设计到开发鉴定弱亲和力化合物的方法都有涉及。本文综述了目前在片段文库设计、片段到先导优化以及筛选技术进展方面的进展。最后，我们将对该领域的未来机遇和挑战进行评论。
