"From Fragments to Pharmaceuticals"
Over the last 20 years Fragment-based drug discovery has developed as an alternative approach for the generation of novel small molecule drug candidates. This approach for lead generation has distinct advantages over conventional bioassay-based screening in that low-affinity but highly ligand efficient fragments can be routinely identified using biophysical techniques such as X-ray crystallography, NMR and calorimetry. These “fragment hits” can then be rapidly optimized for potency and DMPK properties using iterative cycles of medicinal chemistry and structure-based drug design. Using this approach new drug candidates with good ligand efficiencies and optimal drug-like properties can be generated for a range of therapeutics targets, a selection of which will be described in this talk. Another major advantage of Fragment-based discovery resides in the ability to sample chemical space in a highly efficient manner. This has resulted in the discovery of novel allosteric pockets on key protein targets. In this talk I will also describe how fragments can probe the molecular complexity of a protein surface to identify such pockets, which may have a functional role.
8 May 2019, 11:00 (Wednesday, 2nd week, Trinity 2019)
Wellcome Trust Centre for Human Genetics, Headington OX3 7BN
Meeting rooms A & B
Dr Harren Jhoti (Astex Therapeutics Ltd)
Division of Structural Biology
Agata Krupa (Wellcome Centre for Human Genetics, University of Oxford)
Prof Yvonne Jones (University of Oxford),
Prof David Stuart (University of Oxford)
Members of the University only