WORLD CLASS BASIC, TRANSLATIONAL AND CLINICAL RESEARCH

Introduction

The Drug Discovery Unit builds upon fundamental biology discoveries made within the CRUK Manchester Institute, the Manchester Cancer Research Centre, The University of Manchester and the wider cancer research community. Integrating medicinal, computational and synthetic chemistry with in vitro and cellular biology, the centre investigates novel drug discovery targets in an attempt to provide new chemical entities for the treatment of unmet clinical needs in cancer patients.

Initiated in early 2009, the principal aim of the Drug Discovery Unit is to deliver novel treatments into the clinical setting as efficiently as possible. We intend to bridge the translational gap between the fundamental biological research conducted both within the Institute and the wider University community, and the opportunities for clinical application afforded by our proximity to The Christie NHS Foundation Trust. Established as part of the Manchester Cancer Research Centre, the unit has established facilities to enable state-of-the-art biological and clinical target assessment and validation, small molecule drug design and synthesis and the biological evaluation of the resultant compounds.

The Drug Discovery Unit is now actively progressing a portfolio of small molecule projects against a variety of oncology targets.

Selected Publications

Gogola E, Duarte AA, de Ruiter JR, Wiegant WW, Schmid JA, de Bruijn R, James DI, Guerrero Llobet S, Vis DJ, Annunziato S, van den Broek B, Barazas M, Kersbergen A, van de Ven M, Tarsounas M, Ogilvie DJ, van Vugt M, Wessels LFA, Bartkova J, Gromova I, Andújar-Sánchez M, Bartek J, Lopes M, van Attikum H, Borst P, Jonkers J, Rottenberg S. (2018)
Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality.
Cancer Cell 33(6):1078-1093. PubMed abstract

Mould DP, Bremberg U, Jordan AM, Geitmann M, McGonagle AE, Somervaille TCP, Spencer GJ, Ogilvie DJ. (2017)
Development and evaluation of 4-(pyrrolidin-3-yl)benzonitrile derivatives as inhibitors of lysine specific demethylase 1.
Bioorganic & Medicinal Chemistry Letters 27(20):4755-4759. PubMed abstract

Mould DP, Alli C, Bremberg U, Cartic S, Jordan AM, Geitmann M, Maiques-Diaz A, McGonagle AE, Somervaille TCP, Spencer GJ, Turlais F, Ogilvie D. (2017)
Development of (4-Cyanophenyl)glycine Derivatives as Reversible Inhibitors of Lysine Specific Demethylase 1.
Journal of Medicinal Chemistry 60(19):7984-7999. PubMed abstract

James DI, Smith KM, Jordan AM, Fairweather EE, Griffiths LA, Hamilton NS, Hitchin JR, Hutton CP, Jones S, Kelly P, McGonagle AE, Small H, Stowell AI, Tucker J, Waddell ID, Waszkowycz B, Ogilvie DJ. (2016)
First-in-class chemical probes against poly(ADP-ribose) glycohydrolase (PARG) inhibit DNA repair with differential pharmacology to olaparib.
ACS Chemical Biology 11(11):3179-3190. PubMed abstract

Chapman PJ, James DI, Watson AJ, Hopkins GV, Waddell ID, Ogilvie DJ. (2016)
IncucyteDRC: An R package for the dose response analysis of live cell imaging data.
F1000Research 5:962. PubMed abstract

Newton R, Bowler KA, Burns EM, Chapman PJ, Fairweather EE, Fritzl SJ, Goldberg KM, Hamilton NM, Holt SV, Hopkins GV, Jones SD, Jordan AM, Lyons AJ, Nikki March H, McDonald NQ, Maguire LA, Mould DP, Purkiss AG, Small HF, Stowell AI, Thomson GJ, Waddell ID, Waszkowycz B, Watson AJ, Ogilvie DJ. (2016)
The discovery of 2-substituted phenol quinazolines as potent and selective RET kinase inhibitors with improved KDR selectivity.
European Journal of Medicinal Chemistry 112:20-32. PubMed abstract

Watson AJ, Hopkins GV, Hitchin S, Begum H, Jones S, Jordan A, Holt S, March HN, Newton R, Small H, Stowell A, Waddell ID, Waszkowycz B, Ogilvie DJ. (2016)
Identification of selective inhibitors of RET and comparison with current clinical candidates through development and validation of a robust screening cascade.
F1000Research 5:1005. PubMed abstract

Jordan AM, Waddell ID, Ogilvie DJ. (2015)
Rethinking ‘academic’ drug discovery: the Manchester Institute perspective.
Drug Discovery Today 20(5):525-35. PubMed abstract

Raoof A, Depledge P, Hamilton NM, Hamilton NS, Hitchin JR, Hopkins GV, Jordan AM, Maguire LA, McGonagle AE, Mould DP, Rushbrooke M, Small HF, Smith KM, Thomson GJ, Turlais F, Waddell ID, Waszkowycz B, Watson AJ, Ogilvie DJ. (2013)
Toxoflavins and deazaflavins as the first reported selective small molecule inhibitors of tyrosyl-DNA phosphodiesterase II.
Journal of Medicinal Chemistry 56(16):6352-70. PubMed abstract

Harris WJ, Huang X, Lynch JT, Spencer GJ, Hitchin JR, Li Y, Ciceri F, Blaser JG, Greystoke BF, Jordan AM, Miller CJ, Ogilvie DJ, Somervaille TC. (2012)
The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells.
Cancer Cell 21(4):451. PubMed abstract

Hamilton NM, Dawson M, Fairweather E, Hamilton NS, Hitchin JR, James DI, Jones SD, Jordan AM, Lyons AJ, Small HF, Thomson GJ, Waddell ID, Ogilvie DJ. (2012)
Novel steroid inhibitors of glucose-6-phosphate dehydrogenase.
Journal of Medicinal Chemistry 55(9):4431-45. PubMed abstract