Discussion

Over the past decade, fragment-based drug discovery (FBDD) has become a widely accepted tool across industry and academia. At Astex, we have now successfully applied our fragment-based screening approach, PyramidTM, to over 30 targets from a broad range of protein classes. Typically the small molecule fragments we use have MW ~200 and binding affinities between mM weak uM. Subsequently, in the fragments-to-leads stage a detailed structural understanding of the binding interactions between the fragment and its target protein utilizing X-ray crystallography is critical. We monitor the Ligand Efficiency (LE) throughout the optimisation in order to control the chemical properties of the final clinical candidates. This presentation will start with a general overview of the techniques associated with fragment based drug discovery before reviewing specific examples of Astex's FBDD programmes leading to development candidates.