Exploring chemical and biological space: new approaches to drug discovery in oncology


Session type:

Sir Tom Blundell

University of Cambridge, UK


Exploring chemical and biological space: new approaches to drug discovery in oncology

The knowledge of protein targets that is now emerging from high throughput structural proteomics and targeted structural biology programmes has the potential to increase our understanding of human genetic variation, as well as to accelerate drug discovery. Protein structures provide insights into human genetic variation, including both non-synonymous single nucleotide polymorphisms and somatic mutations and their relationships to disease [1]. High-throughput structural analyses can also be used to explore chemical space, to investigate the chemical molecules that proteins might bind. An effective approach is to exploit fragment-screening techniques, which inform not only lead discovery but also optimization of candidate molecules (for a review, see [2]). My talk will focus on efforts in a small company, Astex Therapeutics, and in academia to derive new chemical entities for use in cancer therapy, either against traditional targets like kinases or more challenging ones involving protein-protein interactions by disrupting allostery or co-localisation in signalling and repair pathways . A long-term objective must be to define the chemical space around all macromolecules in man and in pathogens, so as not only to facilitate lead discovery but also to identify potential off-target interactions and minimise side effects.


[1] Worth C.L., Bickerton G.R.J, Schreyer A., Forman, J.R., Cheng T.M.K., Lee S., Gong S., Burke D.F. and Blundell T.L. (2007) Journal Bioinformatics & Computational Biology 5, 1297 - 1318

[2] Congreve M, Murray CW and Blundell TL (2005) Structural Biology and Drug Discovery. Drug Discovery Today 10, 895-907

Declaration of competing interest: Tom Blundell is Co-founder and Board Member of Astex Therapeutics and a member of the Advisory Board of UCB.