From Fragment Screening to Potent Binders: Strategies for Fragment-to-Lead Evolution

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.