Dr Jack 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)
- Gamage, S. A., Giddens, A. C., Tsang, K. Y., Flanagan, J. U., Kendall, J. D., Lee, W.-J., ... Shepherd, P. R. (2017). Synthesis and biological evaluation of sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474. Bioorganic & medicinal chemistry, 25 (20), 5859-5874. 10.1016/j.bmc.2017.09.025
Other University of Auckland co-authors: Gordon Rewcastle, Swarna Gamage, Anna Giddens, Bill Denny, Jackie Kendall, Bruce Baguley, Stephen Jamieson
- Gong, G. Q., Kendall, J. D., Dickson, J. M. J., Rewcastle, G. W., Buchanan, C. M., Denny, W. A., ... Flanagan, J. U. (2017). Combining properties of different classes of PI3Kα inhibitors to understand the molecular features that confer selectivity. The Biochemical journal, 474 (13), 2261-2276. 10.1042/bcj20161098
Other University of Auckland co-authors: Gordon Rewcastle, James Dickson, Christina Buchanan, Bill Denny, Jackie Kendall
- Liew, L. P., Wong, W. W., Singleton, D. C., Jamieson, S. M., Flanagan, J. F., Koumenis, C., & Hay, M. P. (2017). The Development of Hypoxia-selective PERK Inhibitor Prodrugs. Paper presented at 15th International Tumor Microenvironment Workshop, The Palms Hotel and Spa, Miami Beach, Florida. 27 April - 29 April 2017. Related URL.
Other University of Auckland co-authors: Lydia Liew, Way Wong, Dean Singleton, Stephen Jamieson, Michael Hay
- Karunasinghe, N., Masters, J., Flanagan, J. U., & Ferguson, L. R. (2017). Influence of Aldo-keto reductase 1C3 in prostate cancer -a mini review. Current cancer drug targets10.2174/1568009617666170330115722
Other University of Auckland co-authors: Nishi Karunasinghe
- 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 evalution 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