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)
- Trevarton, A. J., Zhou, Y., Yang, D., Rewcastle, G. W., Flanagan, J. U., Braithwaite, A., ... Lasham, A. (2019). Orthogonal assays for the identification of inhibitors of the single-stranded nucleic acid binding protein YB-1. ACTA PHARMACEUTICA SINICA B, 9 (5), 997-1007. 10.1016/j.apsb.2018.12.011
Other University of Auckland co-authors: Annette Lasham, Gordon Rewcastle, Cristin Print
- Gamage, S. A., Spicer, J. A., Tsang, K. Y., O'Connor PD, Flanagan, J. U., Lee, W.-J., ... Rewcastle, G. W. (2019). Synthesis and Evaluation of Imidazo[1,2-a]pyridine Analogues of the ZSTK474 Class of Phosphatidylinositol 3-Kinase Inhibitors. Chemistry, an Asian journal, 14 (8), 1249-1261. 10.1002/asia.201801762
Other University of Auckland co-authors: James Dickson, Bill Denny, Gordon Rewcastle, Swarna Gamage, Julie Spicer, Woo Lee
- Irvine, W. A., Flanagan, J. U., & Allison, J. R. (2019). Computational Prediction of Amino Acids Governing Protein-Membrane Interaction for the PIP3 Cell Signaling System. Structure (London, England : 1993), 27 (2), 371-380.e3. 10.1016/j.str.2018.10.014
Other University of Auckland co-authors: Jane Allison
- Lu, M., Flanagan, J. U., Langley, R. J., Hay, M. P., & Perry, J. K. (2019). Targeting growth hormone function: strategies and therapeutic applications. Signal transduction and targeted therapy, 410.1038/s41392-019-0036-y
Other University of Auckland co-authors: Michael Hay, Ries Langley, Jo Perry
- Gong, G. Q., Wang, K., Dai, X.-C., Zhou, Y., Basnet, R., Chen, Y., ... Flanagan, J. U. (2018). Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds. Acta pharmacologica Sinica, 39 (12), 1902-1912. 10.1038/s41401-018-0087-6
Other University of Auckland co-authors: Christina Buchanan, Woo Lee
- Rewcastle, G. W., Gamage, S. A., Spicer, J. A., Flanagan, J. U., Denny, W. A., & Shepherd, P. R. (15/11/2018). Synthesis and evaluation of imidazo[1,2-a]pyridine analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474. Poster presented at 30th EORTC-NCI-AACR symposium, “Molecular Targets and Cancer Therapeutics.”, Dublin, Ireland 13-16th November 2018.. European Journal of Cancer. 10.1016/S0959-8049(18)31491-6
Other University of Auckland co-authors: Gordon Rewcastle, Swarna Gamage, Julie Spicer, Bill Denny, James Dickson
- Wang, J., Gong, G. Q., Zhou, Y., Lee, W.-J., Buchanan, C. M., Denny, W. A., ... Flanagan, J. U. (2018). High-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds. Acta pharmacologica Sinica, 39 (11), 1816-1822. 10.1038/s41401-018-0057-z
Other University of Auckland co-authors: Gordon Rewcastle, Woo Lee, Christina Buchanan, James Dickson, Bill Denny
- Stevenson, R. J., Azimi, I., Flanagan, J. U., Inserra, M., Vetter, I., Monteith, G. R., & Denny, W. D. (2018). An SAR study of hydroxy-trifluoromethylpyrazolines as inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader assay. Bioorganic and Medicinal Chemistry, 26 (12), 3406-3413. 10.1016/j.bmc.2018.05.012
Other University of Auckland co-authors: Ralph Stevenson, Bill Denny