Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn St., Baltimore, MD 21201, USA.
ChemMedChem. 2021 Mar 3;16(5):725-742. doi: 10.1002/cmdc.202000756. Epub 2020 Dec 16.
Against the challenge of providing personalized cancer care, the development of targeted therapies stands as a promising approach. The discovery of these agents can benefit from fragment-based drug discovery (FBDD) methods that help guide ligand design and provide key structural information on the targets of interest. In particular, nuclear magnetic resonance spectroscopy is a promising biophysical tool in fragment discovery due to its detection capabilities and versatility. This review provides an overview of FBDD, describes the basis of NMR-based fragment screening, summarizes some exciting technical advances reported over the past decades, and closes with a discussion of selected case studies where this technique has been used as part of drug discovery campaigns to produce lead compounds towards the design of anti-cancer targeted therapies.
面对提供个性化癌症护理的挑战，靶向治疗的发展是一种很有前途的方法。这些药物的发现可以受益于基于片段的药物发现 (FBDD) 方法，这些方法有助于指导配体设计，并提供有关目标的关键结构信息。特别是，核磁共振波谱学由于其检测能力和多功能性，是一种很有前途的片段发现生物物理工具。这篇综述概述了 FBDD，描述了基于 NMR 的片段筛选的基础，总结了过去几十年报道的一些令人兴奋的技术进展，并以讨论选定的案例研究结束，其中该技术已被用作药物发现活动的一部分，以产生针对设计抗癌靶向治疗的先导化合物。
