Lavis , Trento , Italy.
Global Discovery Chemistry , Novartis Institutes for Biomedical Research , 4002 Basel , Switzerland.
J Med Chem. 2019 Mar 14;62(5):2218-2244. doi: 10.1021/acs.jmedchem.8b01210. Epub 2018 Oct 29.
Ligand-based fluorine NMR screening has gained popularity in drug discovery projects during the past decade and has become a powerful methodology to produce high quality hits. Its high sensitivity to protein binding makes it particularly suitable for fragment screening, allowing detection and binding strength measurement of very weak affinity ligands. The screening can be performed in direct or competition format, and its versatility allows application to complex biological and chemical systems. As the potential of the methodology has now been recognized and successfully demonstrated in several relevant medicinal chemistry projects, it is now an appropriate time to report the learned lessons and point the way to the future. In this Perspective the principles of the methodology along with several applications to pharmaceutical projects are presented.
基于配体的氟 NMR 筛选在过去十年中在药物发现项目中越来越受欢迎，并且已经成为产生高质量命中物的强大方法。其对蛋白质结合的高灵敏度使其特别适合片段筛选，允许检测和测量非常弱亲和力配体的结合强度。筛选可以直接或竞争格式进行，其多功能性允许应用于复杂的生物和化学系统。由于该方法的潜力现已在几个相关的药物化学项目中得到认可并成功证明，现在是时候报告所学到的经验教训并为未来指明方向了。在这篇观点文章中，介绍了该方法的原理以及对制药项目的几个应用。
