11:30 – 11:45 

Dr Robert Channon:  From Bench to Bedside:  Nucleic Acid Sensors via Paper-Based Oligonucleotide-Templated Reactions

11:45 – 12:00 

Tiffany Chan:  Targeted delivery of therapeutic agents across the blood-brain barrier using focused ultrasound

12:00 – 13:00

Main Visiting Speaker – Dr Tom D. Heightman:  Fragment Based Drug Discovery and Chemical Biology

Abstract:

Fragment based drug discovery at Astex uses X-ray crystallographic and biophysical screening to detect the binding of small molecular fragments. Although such fragments bind with weak affinities, their small size allows them to adopt well aligned orientations that maximize their interaction with the target protein. Selection of fragment hits with vectors suitable for growing and optimization, supported by fast iterative structure-based design, allows potent inhibitors to be constructed with a highly complementary structure to the target protein. The approach allows molecular weight and lipophilicity to be strictly controlled, providing leads with high ligand efficiency, which is of particular importance when addressing challenging targets with dispersed pharmacophores such as protein-protein interactions.

 This talk will describe key aspects of fragment-based drug discovery at Astex, including screening, X-ray structure guided design, ligand conformational analysis in solution, and development of new synthesis methodology for fragment vector growth enablement, illustrated by recent projects which successfully progressed from fragment screens into pre-clinical and clinical drug candidates. The lecture will close with some highlights from recent work to explore a “click and play” approach to chemical biology experiments including cellular imaging, target engagement and in-cell formation of PROTACs.

Biography:

Tom obtained his Chemistry MA at Oxford, and PhD at the ETH Zurich with Prof A. Vasella. In his subsequent 20-year medicinal chemistry career he has made significant contributions to the discovery of over 30 leads and 15 pre-clinical candidates, of which 7 progressed to IND and 5 so far to Phase 2 trials.

• 1998-2008: GlaxoSmithKline in Harlow, UK – positions of increasing responsibility, becoming Head of Lead Discovery for Neurology CEDD 2006-2008.
• 2008-2010: Structural Genomics Consortium at Oxford University, PI for Chemical Biology and Project Manager for SGC’s Epigenetics Chemical Probes Consortium.
• 2011-2019: Astex in Cambridge, UK, VP and Head of Chemistry working on fragment-based drug discovery in oncology and CNS, responsible for all chemistry aspects up to IND.
• 2019 (from July): AstraZeneca, VP Global Head of Oncology Chemistry.
• Fellow of the Royal Society of Chemistry, member of BMCS committee 2005-2013 and Chemistry-Biology Interface Division Council 2011-2017.
• Lecturer at Oxford Life Science Interface DTC 2009-2012 & Wellcome Trust Drug Discovery training course 2010-2018.
• SAB member, Imperial College Chemical Biology CDT.
• Co-authored over 100 publications/patents and delivered over 40 invited lectures.