Dr Jack Urquhart Flanagan
Jack Flanagan obtained his BSc(Hons) in Biochemistry and Molecular Genetics at Victoria University of Wellington, New Zealand, and was awarded a PhD scholarship to study at the John Curtin School of Medical Research, Australian National University, Australia where he investigated structure function relationships for the glutathione transferase class of detoxication enzyme in the laboratory of Prof Philip Board. After a postdoctoral position researching structure function relationships in the major drug metabolising cytochromes P450 under Prof Roland Wolf at the Biomedical Research Centre, University of Dundee, United Kingdom, he took up a Howard Florey Centenary Fellowship at the Institute for Molecular Biosciences, University of Queensland, Australia looking at inhibitor discovery for the human hematopoietic prostaglandin D2 synthase enzyme. Currently a Senior Research Fellow at the Auckland Cancer Society Research Centre, Jack is involved in integrating molecular modelling and virtual screening methods of inhibitor discovery into a number of current medicinal chemistry projects. He is also an Associate Investigator in the Maurice Wilkins Centre for Molecular Biodiscovery.
- Ligand protein interactions
- Molecular Modelling
- Virtual Screening
- Lipid Signalling
- Medicinal Chemistry
Research | Current
- Discovery and development of compounds inhibiting the synthesis of secondary lipid signalling molecules including prostanoids synthesised through the cyclooxygenase pathway, and phosphatidylinositides synthesised by the phosphoinositide 3 kinase family of enzymes.
- Exploration of ligand specificity and inhibitor discovery for hemo-proteins involved in cancer.
- Characterising the molecular basis of ligand recognition by interrogating biological data using analytical Quantitative Structure Activity Relationship techniques that incorporate physico-chemical properties of ligands.
- Molecular docking and virtual screening as methods to identify candidate inhibitors for proteins of interest.
- Fold prediction and comparative modelling of proteins and protein families as a method for hypothesis development about activity differences between isoforms.
Selected publications and creative works (Research Outputs)
- Gong, G. Q., Kendall, J. D., Dickson, J. M., Rewcastle, G. W., Buchanan, C. M., Denny, W. A., ... Flanagan, J. U. (2017). Combining properties of different classes of PI3Kα inhibitors to understand molecular features that confer selectivity. The Biochemical journal10.1042/bcj20161098
Other University of Auckland co-authors: Gordon Rewcastle, James Dickson, Bill Denny
- Copp, J. N., Mowday, A. M., Williams, E. M., Guise, C. P., Ashoorzadeh, A., Sharrock, A. V., ... Ackerley, D. F. (2017). Engineering a Multifunctional Nitroreductase for Improved Activation of Prodrugs and PET Probes for Cancer Gene Therapy. Cell chemical biology, 24 (3), 391-403. 10.1016/j.chembiol.2017.02.005
Other University of Auckland co-authors: Jeffrey Smaill, Christopher Guise, Amir Ashoorzadeh, Adam Patterson, Alexandra Mowday
- Green, T. N., Hamilton, J. R., Morel-Kopp, M.-C., Zheng, Z., Chen, T.-Y. T., Hearn, J. I., ... Barber, P. A. (2017). Inhibition of NMDA receptor function with an anti-GluN1-S2 antibody impairs human platelet function and thrombosis. Platelets, 1-13. 10.1080/09537104.2017.1280149
Other University of Auckland co-authors: Deborah Young, Alan Barber, Maggie Kalev-Zylinska
- Tomek, P., Palmer, B. D., Flanagan, J. U., Sun, C., Raven, E. L., & Ching, L.-M. (2017). Discovery and evaluation of inhibitors to the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1): Probing the active site-inhibitor interactions. European journal of medicinal chemistry, 126, 983-996. 10.1016/j.ejmech.2016.12.029
Other University of Auckland co-authors: Lai-Ming Ching, Petr Tomek, Brian Palmer
- Azimi, I., Flanagan, J. U., Stevenson, R. J., Inserra, M., Vetter, I., Monteith, G. R., & Denny, W. A. (2017). Evaluation of known and novel inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a Fluorescence Imaging Plate Reader assay. Bioorganic & medicinal chemistry, 25 (1), 440-449. 10.1016/j.bmc.2016.11.007
Other University of Auckland co-authors: Bill Denny, Ralph Stevenson
- Mowday, A. M., Ashoorzadeh, A., Williams, E. M., Copp, J. N., Silva, S., Bull, M. R., ... Guise, C. P. (2016). Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy. Biochemical pharmacology, 116, 176-187. 10.1016/j.bcp.2016.07.015
Other University of Auckland co-authors: Alexandra Mowday, Adam Patterson, Bob Anderson, Jeffrey Smaill, Christopher Guise, Maria Abbattista, Amir Ashoorzadeh, Matthew Bull
- Glass, M., Govindpani, K., Furkert, D. P., Hurst, D. P., Reggio, P. H., & Flanagan, J. U. (2016). One for the Price of Two…Are Bivalent Ligands Targeting Cannabinoid Receptor Dimers Capable of Simultaneously Binding to both Receptors?. Trends in pharmacological sciences, 37 (5), 353-363. 10.1016/j.tips.2016.01.010
Other University of Auckland co-authors: Michelle Glass, Daniel Furkert
- Yosaatmadja, Y., Silva, S., Dickson, J. M., Patterson, A. V., Smaill, J. B., Flanagan, J. U., ... Squire, C. J. (2015). Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed. Journal of structural biology, 192 (3), 539-544. 10.1016/j.jsb.2015.10.018
Other University of Auckland co-authors: James Dickson, Christopher Squire, Adam Patterson, Jeffrey Smaill, Yuliana Yosaatmadja, Mark McKeage