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Zinc finger nuclease knock-out of NADPH:cytochrome P450 oxidoreductase (POR) in human tumor cell lines demonstrates that hypoxia-activated prodrugs differ in POR dependence.

Su J, Gu Y, Pruijn FB, Smaill JB, Patterson AV, Guise CP, Wilson WR.

J Biol Chem. 2013 Dec 27;288(52):37138-53. doi: 10.1074/jbc.M113.505222. Epub 2013 Nov 6.


Identification of P450 Oxidoreductase as a Major Determinant of Sensitivity to Hypoxia-Activated Prodrugs.

Hunter FW, Young RJ, Shalev Z, Vellanki RN, Wang J, Gu Y, Joshi N, Sreebhavan S, Weinreb I, Goldstein DP, Moffat J, Ketela T, Brown KR, Koritzinsky M, Solomon B, Rischin D, Wilson WR, Wouters BG.

Cancer Res. 2015 Oct 1;75(19):4211-23. doi: 10.1158/0008-5472.CAN-15-1107. Epub 2015 Aug 21.


Diflavin oxidoreductases activate the bioreductive prodrug PR-104A under hypoxia.

Guise CP, Abbattista MR, Tipparaju SR, Lambie NK, Su J, Li D, Wilson WR, Dachs GU, Patterson AV.

Mol Pharmacol. 2012 Jan;81(1):31-40. doi: 10.1124/mol.111.073759. Epub 2011 Oct 7.


The flavoprotein FOXRED2 reductively activates nitro-chloromethylbenzindolines and other hypoxia-targeting prodrugs.

Hunter FW, Jaiswal JK, Hurley DG, Liyanage HD, McManaway SP, Gu Y, Richter S, Wang J, Tercel M, Print CG, Wilson WR, Pruijn FB.

Biochem Pharmacol. 2014 May 15;89(2):224-35. doi: 10.1016/j.bcp.2014.03.001. Epub 2014 Mar 13.


Identification of human reductases that activate the dinitrobenzamide mustard prodrug PR-104A: a role for NADPH:cytochrome P450 oxidoreductase under hypoxia.

Guise CP, Wang AT, Theil A, Bridewell DJ, Wilson WR, Patterson AV.

Biochem Pharmacol. 2007 Sep 15;74(6):810-20. Epub 2007 Jun 17.


Identification of one-electron reductases that activate both the hypoxia prodrug SN30000 and diagnostic probe EF5.

Wang J, Guise CP, Dachs GU, Phung Y, Hsu AH, Lambie NK, Patterson AV, Wilson WR.

Biochem Pharmacol. 2014 Oct 15;91(4):436-46. doi: 10.1016/j.bcp.2014.08.003. Epub 2014 Aug 15.


Homologous recombination repair-dependent cytotoxicity of the benzotriazine di-N-oxide CEN-209: comparison with other hypoxia-activated prodrugs.

Hunter FW, Wang J, Patel R, Hsu HL, Hickey AJ, Hay MP, Wilson WR.

Biochem Pharmacol. 2012 Mar 1;83(5):574-85. doi: 10.1016/j.bcp.2011.12.005. Epub 2011 Dec 13.


The 2-nitroimidazole EF5 is a biomarker for oxidoreductases that activate the bioreductive prodrug CEN-209 under hypoxia.

Wang J, Foehrenbacher A, Su J, Patel R, Hay MP, Hicks KO, Wilson WR.

Clin Cancer Res. 2012 Mar 15;18(6):1684-95. doi: 10.1158/1078-0432.CCR-11-2296. Epub 2011 Dec 13.


Roles of DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard PR-104A.

Gu Y, Patterson AV, Atwell GJ, Chernikova SB, Brown JM, Thompson LH, Wilson WR.

Mol Cancer Ther. 2009 Jun;8(6):1714-23. doi: 10.1158/1535-7163.MCT-08-1209. Epub 2009 Jun 9.


FSL-61 is a 6-nitroquinolone fluorogenic probe for one-electron reductases in hypoxic cells.

Su J, Guise CP, Wilson WR.

Biochem J. 2013 May 15;452(1):79-86. doi: 10.1042/BJ20121695.


DNA cross-links in human tumor cells exposed to the prodrug PR-104A: relationships to hypoxia, bioreductive metabolism, and cytotoxicity.

Singleton RS, Guise CP, Ferry DM, Pullen SM, Dorie MJ, Brown JM, Patterson AV, Wilson WR.

Cancer Res. 2009 May 1;69(9):3884-91. doi: 10.1158/0008-5472.CAN-08-4023. Epub 2009 Apr 14.


Molecular and cellular pharmacology of the hypoxia-activated prodrug TH-302.

Meng F, Evans JW, Bhupathi D, Banica M, Lan L, Lorente G, Duan JX, Cai X, Mowday AM, Guise CP, Maroz A, Anderson RF, Patterson AV, Stachelek GC, Glazer PM, Matteucci MD, Hart CP.

Mol Cancer Ther. 2012 Mar;11(3):740-51. doi: 10.1158/1535-7163.MCT-11-0634. Epub 2011 Dec 6.


Pre-clinical activity of PR-104 as monotherapy and in combination with sorafenib in hepatocellular carcinoma.

Abbattista MR, Jamieson SM, Gu Y, Nickel JE, Pullen SM, Patterson AV, Wilson WR, Guise CP.

Cancer Biol Ther. 2015;16(4):610-22. doi: 10.1080/15384047.2015.1017171. Epub 2015 Apr 14.


The Role of Bystander Effects in the Antitumor Activity of the Hypoxia-Activated Prodrug PR-104.

Foehrenbacher A, Patel K, Abbattista MR, Guise CP, Secomb TW, Wilson WR, Hicks KO.

Front Oncol. 2013 Oct 7;3:263. doi: 10.3389/fonc.2013.00263. eCollection 2013.


Oxygen dependence and extravascular transport of hypoxia-activated prodrugs: comparison of the dinitrobenzamide mustard PR-104A and tirapazamine.

Hicks KO, Myint H, Patterson AV, Pruijn FB, Siim BG, Patel K, Wilson WR.

Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):560-71.


Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy.

Mowday AM, Ashoorzadeh A, Williams EM, Copp JN, Silva S, Bull MR, Abbattista MR, Anderson RF, Flanagan JU, Guise CP, Ackerley DF, Smaill JB, Patterson AV.

Biochem Pharmacol. 2016 Sep 15;116:176-87. doi: 10.1016/j.bcp.2016.07.015. Epub 2016 Jul 22.


The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3.

Guise CP, Abbattista MR, Singleton RS, Holford SD, Connolly J, Dachs GU, Fox SB, Pollock R, Harvey J, Guilford P, DoƱate F, Wilson WR, Patterson AV.

Cancer Res. 2010 Feb 15;70(4):1573-84. doi: 10.1158/0008-5472.CAN-09-3237. Epub 2010 Feb 9.


P450 oxidoreductase: genetic polymorphisms and implications for drug metabolism and toxicity.

Hart SN, Zhong XB.

Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):439-52. doi: 10.1517/17425255.4.4.439 . Review.


Mechanism of action and preclinical antitumor activity of the novel hypoxia-activated DNA cross-linking agent PR-104.

Patterson AV, Ferry DM, Edmunds SJ, Gu Y, Singleton RS, Patel K, Pullen SM, Hicks KO, Syddall SP, Atwell GJ, Yang S, Denny WA, Wilson WR.

Clin Cancer Res. 2007 Jul 1;13(13):3922-32.


Reductase enzyme expression across the National Cancer Institute Tumor cell line panel: correlation with sensitivity to mitomycin C and EO9.

Fitzsimmons SA, Workman P, Grever M, Paull K, Camalier R, Lewis AD.

J Natl Cancer Inst. 1996 Mar 6;88(5):259-69.


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