www.imperial.ac.uk/medicine/about/institutes/drugdiscoverycentre/cd3/

CD3 - Cancer Drug Design and

Development GroupFocus on reversing resistance to

conventional cancer therapies

Cancer Drug Design Cancer Drug Design and Development Group (CDand Development Group (CD33) )

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

2

Focus on translation

Target PortfolioTarget Portfolio

CRUK training Programme in CRUK training Programme in Medicinal ChemistryMedicinal Chemistry

CDK7CDK7 LRH1LRH1

CDK7CDK7DNMT1DNMT1

FMSFMS

APE1APE1 HDAC4HDAC4

Other Funding Agencies:Other Funding Agencies:EPSRC, AICR, etc.EPSRC, AICR, etc.

EZH2EZH2LRH1LRH1HDAC1HDAC1 Hsp90Hsp90

GrBGrB

Lead Optimisation Target Validation/Hit Identification

CRUK Small CRUK Small Molecule Molecule

Drug Drug Discovery Discovery

ProgrammeProgramme

Key MembersKey Members

Synthetic & Medicinal ChemistryProf. Anthony Barrett FRS FMedSciDr Matthew Fuchter – Also Project Manager (DDC)Dr Chris BraddockProf. Alan ArmstrongProf. Alan SpiveyDr Albert Jaxa-Chamiec (DDC)Dr Caroline Low (DDC molecular modelling)

Pharmacology and imagingProf. Eric AboagyeDr Cathy Tralau-Stewart (DDC)Dr Katie Chapman (DDC)Dr Richard Starkey

Pharma Project ManagementDr Cathy Tralau-Stewart (DDC)

Protein crystallography/structural biologyProf. Paul Freemont

Cancer cell biologyProf. Simak AliProf. Eric LamProf. Laki BuluwelaProf. Hani GabraProf. Philip Ashton-RickardtDr Euan StronachDr Nick Dibb Epigenetics and pharmocodynamicsProf. Robert Brown Clinical developmentProf. Charles Coombes FMedSci

• CDK7:CDK7:•Discovery of the first selective CDK7 inhibitor BS181 Discovery of the first selective CDK7 inhibitor BS181 ((Cancer Res Cancer Res 20092009, 69, 6208, 69, 6208).).•Discovery of a spectrum selective CDK inhibitor with Discovery of a spectrum selective CDK inhibitor with strong growth inhibitory effects strong growth inhibitory effects –– BS194 (J. Med. Chem. BS194 (J. Med. Chem. 20102010, , 53, 850853, 8508).).•Validated RNA PolII P-Ser5 as a useful biomarker for Validated RNA PolII P-Ser5 as a useful biomarker for CDK7 inhibition.CDK7 inhibition.

•LRH1:LRH1:•Gained important new evidence for a major role for Gained important new evidence for a major role for LRH-1 in breast cancer progression (Breast Cancer Res LRH-1 in breast cancer progression (Breast Cancer Res Treat Treat 20102010, DOI: 10.1007/s10549-010-0994-9)., DOI: 10.1007/s10549-010-0994-9).

•Cdc25:Cdc25:•Discovery of the most potent drug-like inhibitors of this Discovery of the most potent drug-like inhibitors of this class of phosphatases known – project now achieved class of phosphatases known – project now achieved independent funding working with DDC.independent funding working with DDC.

•SIRT:SIRT:•Further defined role of isoform selectivity for known Further defined role of isoform selectivity for known SIRT inhibitiors (Mol. Can. Ther. SIRT inhibitiors (Mol. Can. Ther. 20102010, 9, 844)., 9, 844).

Key AchievementsKey Achievements