Eitner Krystian, Koch Uwe
Lead Discovery Center, Emil-Figge-Str. 76a, 44227 Dortmund, Germany.
Mini Rev Med Chem. 2009 Jul;9(8):956-61. doi: 10.2174/138955709788681645.
To be an effective medicine a drug has to possess many attributes to ensure target potency and specificity, lack of toxicity, bioavailability and duration of action. Discovering a compound with these properties is invariably an evolutionary process. Fragment based drug discovery sets out to identify a starting compound by screening a library of small molecules representing fragments which cover the chemical space of drug like matter. Fragment based screening is increasingly used in the pharmaceutical industry in the early stages of lead identification and optimization. We will provide an introduction into this approach and discuss a number of examples which show how fragment based drug discovery has been used in the discovery of starting points for drug discovery programs and in their optimization.
要成为一种有效的药物，一种药物必须具备许多特性，以确保靶点效力和特异性、无毒性、生物利用度和作用持续时间。发现具有这些特性的化合物始终是一个渐进的过程。基于片段的药物发现旨在通过筛选一个代表片段的小分子库来识别起始化合物，这些片段覆盖了类药物物质的化学空间。基于片段的筛选在制药行业的先导化合物识别和优化的早期阶段越来越多地被使用。我们将介绍这种方法，并讨论一些例子，这些例子展示了基于片段的药物发现是如何被用于发现药物研发项目的起始点及其优化过程的。
