CD 3 - Cancer Drug Design and Development Group Focus on reversing resistance to conventional cancer therapies

Cancer Drug Design and Development Group (CD 3 ) 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 Portfolio CRUK training Programme in Medicinal Chemistry CDK7LRH1 CDK7 DNMT1 FMS APE1 HDAC4 Other Funding Agencies: EPSRC, AICR, etc. EZH2 LRH1 HDAC1 Hsp90 GrB Lead Optimisation Target Validation/Hit Identification CRUK Small Molecule Drug Discovery Programme

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 Pharma Project Management Dr Cathy Tralau-Stewart (DDC) 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 Clinical development Prof. Charles Coombes FMedSci

CDK7: CDK7: Discovery of the first selective CDK7 inhibitor BS181 (Cancer Res 2009, 69, 6208). 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). 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. Validated RNA PolII P-Ser5 as a useful biomarker for CDK7 inhibition. LRH1: LRH1: Gained important new evidence for a major role for LRH-1 in breast cancer progression (Breast Cancer Res Treat 2010, DOI: /s ). Gained important new evidence for a major role for LRH-1 in breast cancer progression (Breast Cancer Res Treat 2010, DOI: /s ). Cdc25: Cdc25: Discovery of the most potent drug-like inhibitors of this class of phosphatases known – project now achieved independent funding working with DDC. Discovery of the most potent drug-like inhibitors of this class of phosphatases known – project now achieved independent funding working with DDC. SIRT: SIRT: Further defined role of isoform selectivity for known SIRT inhibitiors (Mol. Can. Ther. 2010, 9, 844). Further defined role of isoform selectivity for known SIRT inhibitiors (Mol. Can. Ther. 2010, 9, 844). Key Achievements