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SUMMARY:Multiprotein assemblies\, structural biology and drug discovery: G
 aining selectivity through allostery - Professor Sir Tom Blundell FRS FMed
 Sci (Department of Biochemistry\, University of Cambridge)
DTSTART:20131030T190000Z
DTEND:20131030T203000Z
UID:TALK47070@talks.cam.ac.uk
CONTACT:Ivan Lam
DESCRIPTION:_This talk is free for members of BioSoc or £2 for non-member
 s. You can also sign up for life membership (£15) or annual membership (
 £10) at this talk._\n\nAlthough investment in pharma for the discovery of
  new medicines has increased exponentially over the past three decades\, t
 his is not reflected in the rate of new drug approvals. Much of the resear
 ch activity has been focused on superfamilies of protein targets\, includi
 ng protein kinases\, proteases and ATPases. This lecture will explore the 
 idea that we should instead target the multiprotein assemblies that regula
 te cell activity. These vary widely within superfamilies and inhibitors ha
 ve the potential to be more selective and therefore less likely to lead to
  off-target effects that contribute to drug failure in development.\n\nI w
 ill focus on the use of fragment-based approaches to making chemical tools
  and candidate therapeutic molecules - an approach pioneered by the compan
 y I cofounded with Chris Abell and Harren Jhoti\, Astex http://www.cam.ac.
 uk/research/news/astex-pharmaceuticals-acquired-by-otsuka.\n\nI will descr
 ibe work in our academic labs on classical allosteric inhibitors - the mod
 ulation by recognition of a site distant from the active site of conformat
 ion in a molecule or assembly - and those that disturb co-location by disr
 upting multi protein assemblies. The targets\, which have been defined by 
 basic research funded by the Wellcome Trust and MRC\, will include cell su
 rface receptors such as FGFR\, a target in cancer\, and Met\, of particula
 r interest in controlling metastasis of tumours. I will also discuss targe
 ting human recombinase\, Rad51\, through interactions with BRCA2\, inhibit
 ors of which would be helpful in modulating DNA repair during chemo- or ra
 diotherapy.\n\nCollaborations have included labs of C Abell and J Skidmore
  in Chemistry\, A Venkitaraman and G McKenzie in Oncology\, E Gherardi in 
 MRC centre and Pavia and Hyvonen in Biochemistry\, Cambridge.
LOCATION:Large Lecture Theatre\, Department of Plant Sciences\, Downing Si
 te
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