"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.
Date: 8 May 2019, 11:00 (Wednesday, 2nd week, Trinity 2019)
Venue: Wellcome Trust Centre for Human Genetics, Headington OX3 7BN
Venue Details: Meeting rooms A & B
Speaker: Dr Harren Jhoti (Astex Therapeutics Ltd)
Organising department: Division of Structural Biology
Organiser: Agata Krupa (Wellcome Centre for Human Genetics, University of Oxford)
Hosts: Prof Yvonne Jones (University of Oxford), Prof David Stuart (University of Oxford)
Part of: Strubi seminars
Booking required?: Not required
Audience: Members of the University only
Editor: Agata Krupa