Background
Michael Hay obtained his BSc (Hons) and PhD in Chemistry from The University of Canterbury, New Zealand. After postdoctoral positions with Professor Steven Ley at Imperial College, London, and Professor Con Cambie at the University of Auckland, Michael was appointed as a Research Fellow in the Centre as a medicinal chemist in 1991. He is currently an Associate Professor in the Centre and an Associate Investigator in the Maurice Wilkins Centre for Molecular Biodiscovery.
Current research interests
Assoc. Prof. Hay has five principal Research Areas that together form a coherent body of work in the area of anti-cancer drug development selectively targeting the tumour microenvironment through bioreductive mechanisms and/or selective target inhibition. My current research interests are:
1 Development of hypoxia-selective cytotoxins and radiation response modifiers based on the 1,2,4-benzotriazine dioxide core.
2 Development of third generation nitroimidazole-based radiosensitizers
3 Design and synthesis of drugs that target hypoxia-inducible factor (HIF-1alpha).
4 Development of novel drugs selectively targeting the loss of the Von Hippel Lindau (VHL) tumour suppressor in tumour cell.
5 Development of antagonists of Adrenomedullin receptor signalling as potential anti-angiogenic agents.
Recent publications
- Wang, J., Foehrenbacher, A., Su, J., Patel, R., Hay, M.P., Hicks, K.O., Wilson, W.R. The 2-nitroimidazole EF5 is a biomarker for oxidoreductases that activate the bioreductive prodrug CEN-209 under hypoxia. Clin. Cancer. Res., 2012, 18, 1684–1695.
- Hunter, F.W., Wang, J., Patel, R., Hsu, H.-L., Hickey, A.J., Hay, M.P., Wilson W.R. Homologous recombination repair-dependent cytotoxicity of the benzotriazine di-N-oxide CEN-209: comparison with other hypoxia-activated prodrugs. Biochem. Pharmacol., 83, 2012, 574–585.
- Hunt, M.A., Li, D., Hay, M.P., Currie, M.J., Robinson, B.A., Patterson, A.V., Dachs, G.U. Characterisation of enzyme prodrug gene therapy combinations in coated spheroids and vascular networks in vitro. J. Gene Med., 2012, 14, 62–74.
- Chan, D.A., Sutphin, P.D., Nguyen, P., Turcotte, S., Lai, E.W., Banh, A., Reynolds, G.E., Chi, J.-T., Wu, J., Solow-Cordero, D.E., Bonnet, M., Flanagan, J.U., Bouley, D.M., Graves, E.E., Denny, W.A., Hay, M.P., Giaccia, A. J. Targeting GLUT1 and the Warburg Effect in Renal Cell Carcinoma by Chemical Synthetic Lethality. Science Trans. Med. 2011, 3, 94ra70.
- Wilson, W.R., Hay, M.P. Targeting hypoxia in cancer therapy. Nature Rev. Cancer, 2011, 11, 393–410 .
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Bonnet, M., Flanagan, J.U., Chan, D.A., Lai, E.W., Nguyen, P., Giaccia, A.J., Hay, M.P. SAR studies of 4-pyridyl heterocyclic anilines that selectively induce autophagic cell death in von Hippel-Lindau-deficient renal cell carcinoma cells. Bioorg. Med. Chem. 2011, 19, 3347–3356.
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Hicks, K.O., Siim, B.G., Jaiswal, J.K., Pruijn, F.B., Fraser, A.M., Patel, R., Hogg, A., Liyanage, H.D.S., Dorie, M.J., Brown, J.M., Denny, W.A., Hay, M.P., Wilson, W.R. Pharmacokinetic/Pharmacodynamic Modeling Identifies SN30000 and SN29751 as Tirapazamine Analogues with Improved Tissue Penetration and Hypoxic Cell Killing in Tumors. Clin. Cancer Res. 2010, 16, 4946–4957.
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Anderson, R.F., Shinde, S.S., Maroz, A., Hay, M.P., Patterson, A.V., Denny, W.A. Characterization of Radicals Formed Following Enzymatic Reduction of 3-Substituted Analogues of the Hypoxia-Activated Cytotoxin 3-Amino-1,2,4 Benzotriazine 1,4-Dioxide (Tirapazamine). J. Am. Chem. Soc. 2010, 132, 2591-2599 .
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Hay, M. P., Turcotte, S., Flanagan, J. U., Bonnet, M., Chan, D. A., Sutphin, P. D., Nguyen, P., Giaccia, A. J., Denny, W. A. 4-Pyridylanilinothiazoles that selectively target von Hippel-Lindau deficient Renal Cell Carcinoma cells by inducing autophagic cell death. J. Med. Chem. 2010, 53, 787-797.
- Shinde, S. S., Hay, M. P., Patterson, A. V., Denny, W. A., Anderson, R. F. Spin-trapping of radicals other than the >OH radical upon reduction of the anticancer agent tirapazamine by cytochrome P450 reductase. J. Am. Chem. Soc. 2009, 131, 14220-14221.
- Shinde, S. S., Maroz, A., Hay, M. P., Anderson, R. F. One-electron reduction potential of the neutral guanyl radical in the GC base pair of duplex DNA. J. Am. Chem. Soc., 2009, 131, 5203-5207.
- Hay, M.P., Hicks, K.O., Pchalek, K., Lee, H.H., Blaser, A., Pruijn, F.B., Anderson, R.F., Shinde, S.S., Wilson, W.R., Denny, W.A. Tricyclic 1,2,4-triazine 1,4-dioxides as hypoxia selective cytotoxins. J. Med. Chem., 2008, 51, 6853-6865.
- Turcotte, S., Sutphin, P.D., Chan, D.A., Hay, M.P., Denny, W.A., Giaccia, A.J. A novel molecule targeting VHL-deficient Renal Cell Carcinoma that induces autophagic cell death. Cancer Cell, 2008, 14, 90–102.
- Pruijn, F.B., Patel, K., Hay, M.P., Wilson, W.R., Hicks K.O. Prediction of Tumour Tissue Diffusion Coefficients of Hypoxia-Activated Prodrugs from Physicochemical Parameters. Aust. J. Chem. 2008, 61, 687–693.
- Hay, M.P., Pchalek, K., Pruijn, F.B., Hicks, K. O., Siim, B. G., Anderson, R. F., Shinde, S. S., Phillips, V., Denny, W.A., Wilson, W.R. Hypoxia-selective 3-alkyl 1,2,4-benzotriazine 1,4-dioxides with antitumor activity: the influence of hydrogen bond donors on extravascular transport. J. Med. Chem. 2007, 50, 6654–6664.
- Hay, M.P., Hicks, K.O., Pruijn, F.B., Pchalek, K., Siim, B.G., Wilson, W.R., Denny, W.A. Pharmacokinetic/pharmacodynamic model-guided identification of hypoxia-selective 1,2,4-benzotriazine 1,4-dioxides with antitumor activity: the role of extravascular transport. J. Med. Chem. 2007, 50, 6392-6404.
- Pchalek, K., Hay, M.P. Stille Coupling Reactions in the Synthesis of Hypoxia-Selective 3-Alkyl-1,2,4-Benzotriazine 1,4-Dioxide Anticancer Agents. J. Org. Chem. 2006, 71, 6530-6535.
- Hicks, K.O., Secomb, T.W., Pruijn, F.B., Hay, M.P., Hsu, R., Brown, J.M., Denny, W.A., Dewhirst, M.W., Wilson, W.R. Use of three-dimensional tissue cultures to model extravascular transport and predict in vivo activity of hypoxia-targeted anticancer drugs. J. Natl Cancer Inst. 2006, 98, 1118-1128.
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