Fragment screening at AstraZeneca: developing the next generation biophysics fragment set
Simon C. C. Lucas, Ulf Börjesson, Mark J. Bostock, John Cuff, Fredrik Edfeldt, Kevin J. Embrey, Per‐Olof Eriksson, Andrea Gohlke, Anders Gunnarson, Michael Lainchbury, Alexander G. Milbradt, Rachel Moore, Philip B. Rawlins, Ian Sinclair, C. W. Stubbs, Richard Storer
Abstract
Fragment based drug discovery is a critical part of the lead generation toolbox and relies heavily on a readily available, high quality fragment library. Over years of use, the AstraZeneca fragment set had become partially depleted and instances of compound deterioration had been found. It was recognised that a redevelopment was required. This provided an opportunity to evolve our screening sets strategy, whilst ensuring that the quality of the fragment set met the robust requirements of fragment screening campaigns. In this communication we share the strategy employed, in particular highlighting two aspects of our approach that we believe others in the community would benefit from, namely that; (i) fragments were selected with input from Medicinal Chemists at an early stage, and (ii) the library was arranged in a layered format to ensure maximum flexibility on a per target basis.