Fragments: past, present and future.

Fragment-based drug discovery has come a long way in a short period of time and is now being used throughout the biopharmaceutical industry. Here we review the origin of the approach, discuss how it is being applied and the prospects for future development. We illustrate this with examples from our own projects where we have found that information from fragments can inform the optimisation of hits identified by other means (e.g. HTS and/or virtual screening) and vice versa. We further discuss that fragment information can also be applied to the discovery of ligands for targets that are not readily amenable to structural analysis by experimentation such as GPCRs, particularly through the application of computational modelling methods.