Research Topics
| M P HaySummaryAffiliation: University of Auckland Country: New Zealand Publications
| Collaborators
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Detail Information
Publications
ZD-0473 AstraZenecaM 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]...- Pharmacokinetic/pharmacodynamic model-guided identification of hypoxia-selective 1,2,4-benzotriazine 1,4-dioxides with antitumor activity: the role of extravascular transportMichael 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.... - Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapyMichael 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.... - Hypoxia-selective 3-alkyl 1,2,4-benzotriazine 1,4-dioxides: the influence of hydrogen bond donors on extravascular transport and antitumor activityMichael 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... 
Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxinsMichael 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....- 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 nitroreductaseMichael 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... - 4-Pyridylanilinothiazoles that selectively target von Hippel-Lindau deficient renal cell carcinoma cells by inducing autophagic cell deathMichael 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... - Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamineMichael 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.... - Nitroarylmethylcarbamate prodrugs of doxorubicin for use with nitroreductase gene-directed enzyme prodrug therapyMichael 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... - Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumorsKevin 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... - Oxidation of 2-deoxyribose by benzotriazinyl radicals of antitumor 3-amino-1,2,4-benzotriazine 1,4-dioxidesSujata 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... - DNA-targeted 1,2,4-benzotriazine 1,4-dioxides: potent analogues of the hypoxia-selective cytotoxin tirapazamineMichael 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... - Selective potentiation of the hypoxic cytotoxicity of tirapazamine by its 1-N-oxide metabolite SR 4317Bronwyn 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... - Extravascular transport of drugs in tumor tissue: effect of lipophilicity on diffusion of tirapazamine analogues in multicellular layer culturesFrederik 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... 
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...- Activation of 3-amino-1,2,4-benzotriazine 1,4-dioxide antitumor agents to oxidizing species following their one-electron reductionRobert 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... - Spin trapping of radicals other than the *OH radical upon reduction of the anticancer agent tirapazamine by cytochrome P450 reductaseSujata 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... - One-electron reduction potential of the neutral guanyl radical in the GC base pair of duplex DNASujata 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... - 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 tirapazamineRobert 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... - Use of three-dimensional tissue cultures to model extravascular transport and predict in vivo activity of hypoxia-targeted anticancer drugsKevin 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... - Complete 1H, 13C and 15N NMR assignment of tirapazamine and related 1,2,4-benzotriazine N-oxidesMaruta 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... - Radical properties governing the hypoxia-selective cytotoxicity of antitumor 3-amino-1,2,4-benzotriazine 1,4-dioxidesRobert 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... - Potentiation of the cytotoxicity of the anticancer agent tirapazamine by benzotriazine N-oxides: the role of redox equilibriaRobert 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... - Stille coupling reactions in the synthesis of hypoxia-selective 3-alkyl-1,2,4-benzotriazine 1,4-dioxide anticancer agentsKarin 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)... - A molecule targeting VHL-deficient renal cell carcinoma that induces autophagySandra 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... - Improved potency of the hypoxic cytotoxin tirapazamine by DNA-targetingYvette 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...