Transcript History of Drug Discovery (a personal view)

CD3 - Cancer Drug Design
and Development Group
Focus on reversing resistance to
conventional
cancer therapies
www.imperial.ac.uk/medicine/about/institutes/drugdiscoverycentre/cd3/
Cancer Drug Design
and Development Group (CD3)
A cross-College Research group focused on the validation of
oncology targets, and the development of leads and
ultimately candidate small molecules for clinical PoC
Major funding from Cancer Research UK:
• CRUK training Programme in Medicinal Chemistry
• CRUK Small Molecule Drug Discovery Programme
Focus on translation
2
Target Portfolio
CRUK training Programme in
Medicinal Chemistry
CDK7
LRH1
CRUK Small
Molecule
Drug
Discovery
Programme
APE1
GrB
HDAC4
EZH2
FMS
CDK7
Lead Optimisation
Other Funding Agencies:
EPSRC, AICR, etc.
HDAC1
LRH1
Target
Validation/Hit
Identification
DNMT1
Hsp90
Key Members
Synthetic & Medicinal Chemistry
Prof. Anthony Barrett FRS FMedSci
Dr Matthew Fuchter –
Also Project Manager (DDC)
Dr Chris Braddock
Prof. Alan Armstrong
Prof. Alan Spivey
Dr Albert Jaxa-Chamiec (DDC)
Dr Caroline Low (DDC molecular
modelling)
Pharmacology and imaging
Prof. Eric Aboagye
Dr Cathy Tralau-Stewart (DDC)
Dr Katie Chapman (DDC)
Dr Richard Starkey
Protein crystallography/structural
biology
Prof. Paul Freemont
Cancer cell biology
Prof. Simak Ali
Prof. Eric Lam
Prof. Laki Buluwela
Prof. Hani Gabra
Prof. Philip Ashton-Rickardt
Dr Euan Stronach
Dr Nick Dibb
Epigenetics and pharmocodynamics
Prof. Robert Brown
Pharma Project Management
Clinical development
Dr Cathy Tralau-Stewart (DDC)
Prof. Charles Coombes FMedSci
Key Achievements
• CDK7:
•Discovery of the first selective CDK7 inhibitor BS181
(Cancer Res 2009, 69, 6208).
•Discovery of a spectrum selective CDK inhibitor with
strong growth inhibitory effects – BS194 (J. Med.
Chem. 2010, 53, 8508).
•Validated RNA PolII P-Ser5 as a useful biomarker for
CDK7 inhibition.
•LRH1:
•Gained important new evidence for a major role for
LRH-1 in breast cancer progression (Breast Cancer Res
Treat 2010, DOI: 10.1007/s10549-010-0994-9).
•Cdc25:
•Discovery of the most potent drug-like inhibitors of this
class of phosphatases known – project now achieved
independent funding working with DDC.
•SIRT:
•Further defined role of isoform selectivity for known
SIRT inhibitiors (Mol. Can. Ther. 2010, 9, 844).