M P Hay

Summary

Affiliation: University of Auckland
Country: New Zealand

Publications

  1. ncbi request reprint Hypoxia-directed drug strategies to target the tumor microenvironment
    Michael P Hay
    Auckland Cancer Society Research Centre, The University of Auckland, 92019, Auckland, 1142, New Zealand
    Adv Exp Med Biol 772:111-45. 2014
  2. pmc Pseudomonas aeruginosa NfsB and nitro-CBI-DEI--a promising enzyme/prodrug combination for gene directed enzyme prodrug therapy
    Laura K Green
    School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, New Zealand
    Mol Cancer 12:58. 2013
  3. pmc 4-Pyridylanilinothiazoles that selectively target von Hippel-Lindau deficient renal cell carcinoma cells by inducing autophagic cell death
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Med Chem 53:787-97. 2010
  4. pmc Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
    J Med Chem 51:6853-65. 2008
  5. ncbi request reprint Hypoxia-selective 3-alkyl 1,2,4-benzotriazine 1,4-dioxides: the influence of hydrogen bond donors on extravascular transport and antitumor activity
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand
    J Med Chem 50:6654-64. 2007
  6. ncbi request reprint Pharmacokinetic/pharmacodynamic model-guided identification of hypoxia-selective 1,2,4-benzotriazine 1,4-dioxides with antitumor activity: the role of extravascular transport
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1003, New Zealand
    J Med Chem 50:6392-404. 2007
  7. ncbi request reprint ZD-0473 AstraZeneca
    M P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
    Curr Opin Investig Drugs 1:263-6. 2000
  8. ncbi request reprint Nitroarylmethylcarbamate prodrugs of doxorubicin for use with nitroreductase gene-directed enzyme prodrug therapy
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    Bioorg Med Chem 13:4043-55. 2005
  9. ncbi request reprint Structure-activity relationships for 4-nitrobenzyl carbamates of 5-aminobenz[e]indoline minor groove alkylating agents as prodrugs for GDEPT in conjunction with E. coli nitroreductase
    Michael P Hay
    Auckland Cancer Society Research Laboratory, Faculty of Medical and Health Science, The University of Auckland, Private Bag 92019, New Zealand
    J Med Chem 46:2456-66. 2003
  10. ncbi request reprint Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamine
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Med Chem 46:169-82. 2003

Collaborators

Detail Information

Publications28

  1. ncbi request reprint Hypoxia-directed drug strategies to target the tumor microenvironment
    Michael P Hay
    Auckland Cancer Society Research Centre, The University of Auckland, 92019, Auckland, 1142, New Zealand
    Adv Exp Med Biol 772:111-45. 2014
    ..These projects are discussed in the context of hypoxia-directed drug discovery. ..
  2. pmc Pseudomonas aeruginosa NfsB and nitro-CBI-DEI--a promising enzyme/prodrug combination for gene directed enzyme prodrug therapy
    Laura K Green
    School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, New Zealand
    Mol Cancer 12:58. 2013
    ..However, relative to some other nitroaromatic prodrugs, nitro-CBI-DEI is a poor substrate for E. coli NfsB. To address this limitation we evaluated other nitroreductase candidates from E. coli and Pseudomonas aeruginosa...
  3. pmc 4-Pyridylanilinothiazoles that selectively target von Hippel-Lindau deficient renal cell carcinoma cells by inducing autophagic cell death
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Med Chem 53:787-97. 2010
    ..Examples probing this domain validated this approach and may provide the opportunity to develop this novel chemotype as a targeted approach to the treatment of RCC...
  4. pmc Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
    J Med Chem 51:6853-65. 2008
    ....
  5. ncbi request reprint Hypoxia-selective 3-alkyl 1,2,4-benzotriazine 1,4-dioxides: the influence of hydrogen bond donors on extravascular transport and antitumor activity
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand
    J Med Chem 50:6654-64. 2007
    ..This identified four novel 3-alkyl BTOs providing greater clonogenic killing of hypoxic cells than TPZ at equivalent host toxicity, with the 6-morpholinopropyloxy-BTO 22 being 3-fold more active...
  6. ncbi request reprint Pharmacokinetic/pharmacodynamic model-guided identification of hypoxia-selective 1,2,4-benzotriazine 1,4-dioxides with antitumor activity: the role of extravascular transport
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1003, New Zealand
    J Med Chem 50:6392-404. 2007
    ....
  7. ncbi request reprint ZD-0473 AstraZeneca
    M P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
    Curr Opin Investig Drugs 1:263-6. 2000
    ..In June 2000, Deutsche Bank predicted sales of US $15 million in 2003 [374500]. In March 1999, Lehman Brothers predicted a 15% probability that the drug would reach worldwide markets, and be launched onto the market in 2003 [336599]...
  8. ncbi request reprint Nitroarylmethylcarbamate prodrugs of doxorubicin for use with nitroreductase gene-directed enzyme prodrug therapy
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    Bioorg Med Chem 13:4043-55. 2005
    ..This lack of activity in tumours, despite potent and selective activity in culture, indicates that pharmacokinetic optimization is needed to achieve in vivo efficacy against solid tumours with this new class of NTR prodrugs...
  9. ncbi request reprint Structure-activity relationships for 4-nitrobenzyl carbamates of 5-aminobenz[e]indoline minor groove alkylating agents as prodrugs for GDEPT in conjunction with E. coli nitroreductase
    Michael P Hay
    Auckland Cancer Society Research Laboratory, Faculty of Medical and Health Science, The University of Auckland, Private Bag 92019, New Zealand
    J Med Chem 46:2456-66. 2003
    ..These results suggest that useful GDEPT prodrugs based on the 4-nitrobenzyl carbamate and 5-aminobenz[e]indoline motifs may be developed if optimization of pharmacokinetics can be addressed...
  10. ncbi request reprint Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamine
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Med Chem 46:169-82. 2003
    ....
  11. ncbi request reprint Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Med Chem 46:5533-45. 2003
    ....
  12. ncbi request reprint Oxidation of 2-deoxyribose by benzotriazinyl radicals of antitumor 3-amino-1,2,4-benzotriazine 1,4-dioxides
    Sujata S Shinde
    Department of Chemistry and Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1, New Zealand
    J Am Chem Soc 126:7865-74. 2004
    ..1.24 v...
  13. ncbi request reprint DNA-targeted 1,2,4-benzotriazine 1,4-dioxides: potent analogues of the hypoxia-selective cytotoxin tirapazamine
    Michael P Hay
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Med Chem 47:475-88. 2004
    ..The data confirm that DNA targeting is a useful concept for increasing potency while maintaining hypoxic selectivity and provide a direction for the further development of DNA-targeted analogues of TPZ...
  14. pmc Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumors
    Kevin O Hicks
    Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand
    Clin Cancer Res 16:4946-57. 2010
    ..Here, we identify improved TPZ analogues by using a spatially resolved pharmacokinetic/pharmacodynamic (SR-PKPD) model that considers tissue penetration explicitly during lead optimization...
  15. ncbi request reprint Selective potentiation of the hypoxic cytotoxicity of tirapazamine by its 1-N-oxide metabolite SR 4317
    Bronwyn G Siim
    Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand
    Cancer Res 64:736-42. 2004
    ..This study demonstrates that benzotriazine mono-N-oxides have potential use for improving the therapeutic utility of TPZ as a hypoxic cytotoxin in cancer treatment...
  16. ncbi request reprint Activation of 3-amino-1,2,4-benzotriazine 1,4-dioxide antitumor agents to oxidizing species following their one-electron reduction
    Robert F Anderson
    Department of Chemistry and Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, New Zealand
    J Am Chem Soc 125:748-56. 2003
    ..94 to 1.31 V. The benzotriazinyl radical of tirapazamine was found to oxidize dGMP and 2-deoxyribose with rate constants of (1.4 +/- 0.2) x 10(8) M(-)(1) s(-)(1) and (3.7 +/- 0.5) x 10(6) M(-)(1) s(-)(1), respectively...
  17. ncbi request reprint Spin trapping of radicals other than the *OH radical upon reduction of the anticancer agent tirapazamine by cytochrome P450 reductase
    Sujata S Shinde
    Department of Chemistry and Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Am Chem Soc 131:14220-1. 2009
    ..The multicentered nature of this nitrogen-centered radical spectrum provides support for the formation of a benzotriazinyl radical following one-electron reduction of this class of bioreductive drug...
  18. pmc One-electron reduction potential of the neutral guanyl radical in the GC base pair of duplex DNA
    Sujata S Shinde
    Department of Chemistry and Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Am Chem Soc 131:5203-7. 2009
    ..The one-electron reduction potential, E(7), of the neutral guanyl radical in the GC base pair is determined for the first time as 1.22 +/- 0.02 V, from both absorption and kinetic data...
  19. doi request reprint Characterization of radicals formed following enzymatic reduction of 3-substituted analogues of the hypoxia-selective cytotoxin 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine)
    Sujata S Shinde
    Department of Chemistry and Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Am Chem Soc 132:2591-9. 2010
    ..The identification of a range of oxidizing radicals in the metabolism of the BTO compounds gives a new insight into the mechanism by which these HSPs can cause a wide variety of damage to biological targets such as DNA...
  20. ncbi request reprint Complete 1H, 13C and 15N NMR assignment of tirapazamine and related 1,2,4-benzotriazine N-oxides
    Maruta Boyd
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    Magn Reson Chem 44:948-54. 2006
    ..The combination of 13C and 15N NMR provides an unambiguous method for assigning the 1H and 13C resonances of N-oxides of 1,2,4-benzotriazines...
  21. ncbi request reprint Enhanced conversion of DNA radical damage to double strand breaks by 1,2,4-benzotriazine 1,4-dioxides linked to a DNA binder compared to tirapazamine
    Robert F Anderson
    Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland 1, New Zealand
    Chem Res Toxicol 16:1477-83. 2003
    ..The targeting of benzotriazine 1,4-dioxide analogues to DNA by appending binding units to the compounds thus represents an efficient system for inducing strand breaks in DNA...
  22. ncbi request reprint Use of three-dimensional tissue cultures to model extravascular transport and predict in vivo activity of hypoxia-targeted anticancer drugs
    Kevin O Hicks
    Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Natl Cancer Inst 98:1118-28. 2006
    ..We tested whether a three-dimensional pharmacokinetic/pharmacodynamic (PK/PD) model based on a representative mapped tumor microvascular network could predict the therapeutic activity of anticancer drugs in mouse xenograft tumors...
  23. ncbi request reprint Potentiation of the cytotoxicity of the anticancer agent tirapazamine by benzotriazine N-oxides: the role of redox equilibria
    Robert F Anderson
    Department of Chemistry and Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1, New Zealand
    J Am Chem Soc 128:245-9. 2006
    ..The E(1) values of the 1,4-dioxides and 1-oxide compounds govern the degree of potentiation of the initial radical damage once formed...
  24. ncbi request reprint Radical properties governing the hypoxia-selective cytotoxicity of antitumor 3-amino-1,2,4-benzotriazine 1,4-dioxides
    Robert F Anderson
    Department of Chemistry, University of Auckland, Private Bag 92019, Auckland, New Zealand
    Org Biomol Chem 3:2167-74. 2005
    ..It is concluded that maximizing the differential ratio between these two controlling parameters, in combination with necessary pharmacological aspects, will lead to more efficacious anticancer bioreductive drugs...
  25. ncbi request reprint Extravascular transport of drugs in tumor tissue: effect of lipophilicity on diffusion of tirapazamine analogues in multicellular layer cultures
    Frederik B Pruijn
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    J Med Chem 48:1079-87. 2005
    ..This study shows that simple monosubstitution of TPZ can alter log P enough to markedly improve extravascular transport and activity against target cells, especially if rates of metabolic activation are also optimized...
  26. ncbi request reprint Stille coupling reactions in the synthesis of hypoxia-selective 3-alkyl-1,2,4-benzotriazine 1,4-dioxide anticancer agents
    Karin Pchalek
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
    J Org Chem 71:6530-5. 2006
    ..The application of microwave-assisted synthesis extended the range of substituted BTOs available for SAR studies and provided an efficient, scalable synthesis of the investigational anticancer agent, SN29751 (1)...
  27. pmc A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy
    Sandra Turcotte
    Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cancer Cell 14:90-102. 2008
    ..Thus, we have found a small molecule that selectively induces cell death in VHL-deficient cells, representing a paradigm shift for targeted therapy...
  28. pmc Improved potency of the hypoxic cytotoxin tirapazamine by DNA-targeting
    Yvette M Delahoussaye
    Department of Radiation Oncology, Stanford University School of Medicine, 269 Campus Drive, CCSR 1255, Stanford, CA 94305 5152, USA
    Biochem Pharmacol 65:1807-15. 2003
    ..These results show the promise of DNA-targeting of TPZ to produce a DNA compound with greater clinical efficacy than TPZ itself...