nitroreductases

Summary

Summary: Enzymes which reduce nitro groups (NITRO COMPOUNDS) and other nitrogenous compounds.

Top Publications

  1. ncbi Flavin thermodynamics explain the oxygen insensitivity of enteric nitroreductases
    Ronald L Koder
    Department of Chemistry, The University of Kentucky, 106 Chemistry Physics Building, Lexington, Kentucky 40502, USA
    Biochemistry 41:14197-205. 2002
  2. pmc Targeted ablation of beta cells in the embryonic zebrafish pancreas using E. coli nitroreductase
    Harshan Pisharath
    Department of Comparative Medicine, Johns Hopkins School of Medicine, 720 Rutland Avenue, Ross 771, Baltimore, MD 21205, USA
    Mech Dev 124:218-29. 2007
  3. pmc Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites
    Belinda S Hall
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    J Biol Chem 286:13088-95. 2011
  4. pmc Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation
    Belinda S Hall
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom
    Antimicrob Agents Chemother 56:115-23. 2012
  5. pmc A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes
    Shane R Wilkinson
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Proc Natl Acad Sci U S A 105:5022-7. 2008
  6. pmc Nitroreductase-mediated cell/tissue ablation in zebrafish: a spatially and temporally controlled ablation method with applications in developmental and regeneration studies
    Silvia Curado
    Department of Biochemistry and Biophysics, Program in Developmental Biology, Liver Center, Diabetes Center and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94158 2324, USA
    Nat Protoc 3:948-54. 2008
  7. pmc Structure of Ddn, the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis involved in bioreductive activation of PA-824
    Susan E Cellitti
    Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 1125, USA
    Structure 20:101-12. 2012
  8. pmc Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6
    Nicola Baker
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Biochem Parasitol 176:55-7. 2011
  9. ncbi Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954
    G A Prosser
    School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, New Zealand
    Biochem Pharmacol 79:678-87. 2010
  10. pmc E. coli NfsA: an alternative nitroreductase for prodrug activation gene therapy in combination with CB1954
    S O Vass
    Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK
    Br J Cancer 100:1903-11. 2009

Research Grants

Detail Information

Publications173 found, 100 shown here

  1. ncbi Flavin thermodynamics explain the oxygen insensitivity of enteric nitroreductases
    Ronald L Koder
    Department of Chemistry, The University of Kentucky, 106 Chemistry Physics Building, Lexington, Kentucky 40502, USA
    Biochemistry 41:14197-205. 2002
    Bacterial nitroreductases are NAD(P)H-dependent flavoenzymes which catalyze the oxygen-insensitive reduction of nitroaromatics, quinones, and riboflavin derivatives...
  2. pmc Targeted ablation of beta cells in the embryonic zebrafish pancreas using E. coli nitroreductase
    Harshan Pisharath
    Department of Comparative Medicine, Johns Hopkins School of Medicine, 720 Rutland Avenue, Ross 771, Baltimore, MD 21205, USA
    Mech Dev 124:218-29. 2007
    ....
  3. pmc Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites
    Belinda S Hall
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    J Biol Chem 286:13088-95. 2011
    ..These experiments indicate that the basis for the selectivity of nifurtimox against T. brucei lies in the expression of a parasite-encoded type I nitroreductase...
  4. pmc Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation
    Belinda S Hall
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom
    Antimicrob Agents Chemother 56:115-23. 2012
    ....
  5. pmc A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes
    Shane R Wilkinson
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Proc Natl Acad Sci U S A 105:5022-7. 2008
    ..This potential for drug resistance by a simple mechanism has important implications, because nifurtimox is currently undergoing phase III clinical trials against African trypanosomiasis...
  6. pmc Nitroreductase-mediated cell/tissue ablation in zebrafish: a spatially and temporally controlled ablation method with applications in developmental and regeneration studies
    Silvia Curado
    Department of Biochemistry and Biophysics, Program in Developmental Biology, Liver Center, Diabetes Center and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94158 2324, USA
    Nat Protoc 3:948-54. 2008
    ..Using this protocol, cell ablation can be achieved in 12-72 h, depending on the transgenic line used, and recovery initiates within the following 24 h...
  7. pmc Structure of Ddn, the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis involved in bioreductive activation of PA-824
    Susan E Cellitti
    Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 1125, USA
    Structure 20:101-12. 2012
    ..The proposed orientation of the tail of PA-824 toward the N terminus of Ddn is consistent with current structure-activity relationship data...
  8. pmc Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6
    Nicola Baker
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Biochem Parasitol 176:55-7. 2011
    ..Thus, bloodstream-form T. brucei RNAi libraries present a versatile tool for selective genetic screening and for the rapid identification of drug-activation, uptake and potential resistance mechanisms...
  9. ncbi Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954
    G A Prosser
    School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, New Zealand
    Biochem Pharmacol 79:678-87. 2010
    ..In addition, we identify two novel E. coli NTRs, AzoR and NemA, that have not previously been characterized in the context of nitroaromatic prodrug activation...
  10. pmc E. coli NfsA: an alternative nitroreductase for prodrug activation gene therapy in combination with CB1954
    S O Vass
    Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK
    Br J Cancer 100:1903-11. 2009
    ..NfsA is also more effective than NfsB for cell sensitisation to nitrofurans and to a selection of alternative, dinitrobenzamide mustard (DNBM) prodrugs...
  11. pmc Substrate specificity of the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis responsible for the bioreductive activation of bicyclic nitroimidazoles
    Meera Gurumurthy
    Novartis Institute for Tropical Diseases, Singapore, Singapore
    FEBS J 279:113-25. 2012
    ..The results presented provide insight into the biochemical mechanism of reduction and elucidate structural features important for understanding substrate binding...
  12. ncbi Crystal structure of FMN-dependent nitroreductase from Escherichia coli B: a prodrug-activating enzyme
    G N Parkinson
    CRC Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB, United Kingdom
    J Med Chem 43:3624-31. 2000
    ..The structure of the substrate binding pocket has been used to examine substrate specificity and enzyme kinetics for prodrugs used in antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT)...
  13. pmc Evidence for lateral transfer of genes encoding ferredoxins, nitroreductases, NADH oxidase, and alcohol dehydrogenase 3 from anaerobic prokaryotes to Giardia lamblia and Entamoeba histolytica
    Julie E J Nixon
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Eukaryot Cell 1:181-90. 2002
    ..giardial and amebic 6-kDa ferredoxins, ferredoxin-nitroreductase fusion proteins, and oxygen-insensitive nitroreductases each tentatively supported the lateral transfer hypothesis...
  14. ncbi Type I nitroreductases in soil enterobacteria reduce TNT (2,4,6,-trinitrotoluene) and RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine)
    C L Kitts
    Environmental Biotechnology Institute, California Polytechnic State University, San Luis Obispo 93407, USA
    Can J Microbiol 46:278-82. 2000
    ..morganii. We conclude that a type I nitroreductase present in these two enteric bacteria was responsible for the nitroreduction of both types of explosive...
  15. ncbi Expression and characterization of the TNT nitroreductase of Pseudomonas sp. HK-6 in Escherichia coli
    Bheong Uk Lee
    Kosin University, Busan, 606 701, Republic of Korea
    Curr Microbiol 56:386-90. 2008
    ..Even after 20 days, only approximately 50% of the 0.5 mM TNT was degraded by the pnrB mutant. These results illustrate that pnrB may perform a crucial role in the TNT degradation pathway of the HK-6 strain...
  16. ncbi uvrB gene deletion enhances SOS chromotest sensitivity for nitroreductases that preferentially generate the 4-hydroxylamine metabolite of the anti-cancer prodrug CB1954
    G A Prosser
    School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, New Zealand
    J Biotechnol 150:190-4. 2010
    ..We describe here two efficient and previously uncharacterized nitroreductases, YfkO from Bacillus subtilis which reduces CB1954 exclusively at the 4-NO(2) position, and NfsA from ..
  17. pmc Chloramphenicol is a substrate for a novel nitroreductase pathway in Haemophilus influenzae
    Arnold L Smith
    Microbial Pathogens Program, Seattle Biomedical Research Institute, Seattle, WA 98109 5219, USA
    Antimicrob Agents Chemother 51:2820-9. 2007
    ..influenzae and Neisseria species is unknown. Further understanding of the H. influenzae chloramphenicol reduction pathway will contribute to our knowledge of the diversity of prokaryotic nitroreductase mechanisms...
  18. pmc Oxygen-insensitive nitroreductases NfsA and NfsB of Escherichia coli function under anaerobic conditions as lawsone-dependent Azo reductases
    Jorg Rau
    Institut fur Mikrobiologie, Universitat Stuttgart, Stuttgart, Germany
    Appl Environ Microbiol 69:3448-55. 2003
    ..In addition it was proven that also a second oxygen-insensitive nitroreductase of E. coli (NfsA) is able to reduce lawsone and thus to function under adequate conditions as quinone-dependent azo reductase...
  19. ncbi Phytodetoxification of TNT by transgenic plants expressing a bacterial nitroreductase
    N Hannink
    Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, UK
    Nat Biotechnol 19:1168-72. 2001
    ..Our work suggests that expression of nitroreductase (NR) in plants suitable for phytoremediation could facilitate the effective cleanup of sites contaminated with high levels of explosives...
  20. ncbi Fluorogenic substrates for the detection of microbial nitroreductases
    A L James
    Department of Chemical and Life Sciences, University of Northumbria, Newcastle upon Tyne, NE1 8ST, UK
    Lett Appl Microbiol 33:403-8. 2001
    AIMS: To synthesize and evaluate fluorogenic substrates for the detection of microbial nitroreductases. These substrates, all based on 7-nitrocoumarin, may be reduced to form fluorescent aminocoumarins...
  21. ncbi Nitroreductase-based GDEPT
    William A Denny
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, Auckland 1000, New Zealand
    Curr Pharm Des 8:1349-61. 2002
    b>Nitroreductases that metabolise aromatic nitro groups to hydroxylamines are attractive as enzymes for GDEPT because of the very large electronic change that this metabolism generates, providing an efficient switch that can be exploited ..
  22. ncbi Is the molecular basis of metronidazole resistance in microaerophilic organisms understood?
    George L Mendz
    Dept of Biochemistry and Molecular Genetics, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia
    Trends Microbiol 10:370-5. 2002
    ..This review presents the status of our current knowledge of metronidazole resistance and outlines reasons to explain some of the conflicting evidence and controversy in the interpretation of results in this area...
  23. pmc Mechanism of cell death induced by the novel enzyme-prodrug combination, nitroreductase/CB1954, and identification of synergism with 5-fluorouracil
    D H Palmer
    CR UK Institute for Cancer Studies, Clinical Research Block, University of Birmingham, Birmingham B15 2TA, UK
    Br J Cancer 89:944-50. 2003
    ..These data will facilitate the further development and future clinical trial design of this novel therapy...
  24. pmc Construction of Escherichia coli strains for conversion of nitroacetophenones to ortho-aminophenols
    Venkateswarlu Kadiyala
    Air Force Research Laboratory, Tyndall Air Force Base, Florida 32403 5323, USA
    Appl Environ Microbiol 69:6520-6. 2003
    ....
  25. pmc Characterization of the NAD(P)H oxidase and metronidazole reductase activities of the RdxA nitroreductase of Helicobacter pylori
    Igor N Olekhnovich
    Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
    FEBS J 276:3354-64. 2009
    ..Unlike other nitroreductases, His6-RdxA exhibited potent NAD(P)H-oxidase activity (k(cat) = 2...
  26. ncbi 2-Arylbenzothiazole, benzoxazole and benzimidazole derivatives as fluorogenic substrates for the detection of nitroreductase and aminopeptidase activity in clinically important bacteria
    Marie Cellier
    Research and Development Microbiology, bioMerieux SA, 3 route de Port Michaud, 38 390 La Balme Les Grottes, France
    Bioorg Med Chem 19:2903-10. 2011
    ..The growth of Gram positive bacteria was generally inhibited by these substrates but fluorescent colonies were produced with the majority of Gram negative bacteria tested...
  27. ncbi Physical characterisation of the Escherichia coli B gene encoding nitroreductase and its over-expression in Escherichia coli K12
    N P Michael
    Department of Molecular Microbiology, Centre for Applied Microbiology and Research, Salisbury, Wiltshire, UK
    FEMS Microbiol Lett 124:195-202. 1994
    ..Substitution of the nfrB ribosome binding site with that of the E. coli lacZ gene reduced production levels of nitroreductase. The sequenced region also contained two incomplete open reading frames of unknown function...
  28. pmc A redox basis for metronidazole resistance in Helicobacter pylori
    N O Kaakoush
    School of Medical Sciences, The University of New South Wales, Sydney, New South Wales 2052, Australia
    Antimicrob Agents Chemother 53:1884-91. 2009
    ..The data suggested that metronidazole resistance involved more complex metabolic changes than specific gene mutations, and they provided evidence of a role for the intracellular redox potential in the development of resistance...
  29. ncbi Immune enhancement of nitroreductase-induced cytotoxicity: studies using a bicistronic adenovirus vector
    Nicola K Green
    Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Oxford, United Kingdom
    Int J Cancer 104:104-12. 2003
    ....
  30. ncbi Creation and screening of a multi-family bacterial oxidoreductase library to discover novel nitroreductases that efficiently activate the bioreductive prodrugs CB1954 and PR-104A
    Gareth A Prosser
    School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, New Zealand
    Biochem Pharmacol 85:1091-103. 2013
    ..The most catalytically efficient nitroreductases were found in the NfsA and NfsB enzyme families, with NfsA homologues generally more active than NfsB...
  31. ncbi NADH oxidase activity of Bacillus subtilis nitroreductase NfrA1: insight into its biological role
    Sylvie Cortial
    Institut de Chimie des Substances Naturelles ICSN, CNRS UPR 2301, Gif sur Yvette, France
    FEBS Lett 584:3916-22. 2010
    ..Finally, we showed that NfrA1 is able to rapidly scavenge H(2)O(2) produced during the oxidative process or added exogenously...
  32. ncbi Comparison of four microbial enzymes in Clostridia and Bacteroides isolated from human feces
    Joe Nakamura
    4th Department of Internal Medicine, Tokyo Medical University, Japan
    Microbiol Immunol 46:487-90. 2002
    ..05) higher than that in the clostridia isolated from healthy subjects and the subjects given high beef diets. However, the activities of some microorganisms tested showed marked differences in each strain...
  33. pmc Structure-activity relationships of antitubercular nitroimidazoles. 1. Structural features associated with aerobic and anaerobic activities of 4- and 5-nitroimidazoles
    Pilho Kim
    Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 52:1317-28. 2009
    ..Aerobic activity appears to be correlated with efficiency as a substrate for Ddn, suggesting a means of structure-based optimization of improved nitroimidazoles...
  34. ncbi Trypanocidal drugs: mechanisms, resistance and new targets
    Shane R Wilkinson
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK
    Expert Rev Mol Med 11:e31. 2009
    ....
  35. pmc Exploiting the drug-activating properties of a novel trypanosomal nitroreductase
    Belinda S Hall
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom
    Antimicrob Agents Chemother 54:1193-9. 2010
    ..We conclude that halogenated nitrobenzylphosphoramide mustards represent a novel class of antitrypanosomal agents, and their efficacy validates the strategy of specifically targeting NTR activity to develop new therapeutics...
  36. ncbi Selective ablation of olfactory receptor neurons without functional impairment of vomeronasal receptor neurons in OMP-ntr transgenic mice
    Dan Ma
    Sub Department of Animal Behaviour, University of Cambridge, High Street, Madingley, CB3 8AA, UK
    Eur J Neurosci 16:2317-23. 2002
    ..This novel technique could potentially be applied to selectively ablate olfactory receptor neurons expressing a particular olfactory receptor by linking its expression to that of the nitroreductase enzyme...
  37. pmc Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases)
    Dibyarupa Pal
    Department of Biotechnology, Indian Institute of Technology, Kharagpur, West Bengal
    Antimicrob Agents Chemother 53:458-64. 2009
    ..Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased ..
  38. ncbi Reduction of polynitroaromatic compounds: the bacterial nitroreductases
    María Dolores Roldán
    Departamento de Bioquimica y Biologia Molecular, Campus de Rabanales, Universidad de Cordoba, Cordoba, Spain
    FEMS Microbiol Rev 32:474-500. 2008
    ..Bacterial nitroreductases are flavoenzymes that catalyze the NAD(P)H-dependent reduction of the nitro groups on nitroaromatic and ..
  39. ncbi Nitroreductase: a prodrug-activating enzyme for cancer gene therapy
    Peter F Searle
    Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham
    Clin Exp Pharmacol Physiol 31:811-6. 2004
    ..These can provide improved cell sensitization to CB1954. Combinations of these are being tested. 7. The basis for a positive selection for improved NTR variants has been demonstrated...
  40. ncbi Kinetic and structural characterisation of Escherichia coli nitroreductase mutants showing improved efficacy for the prodrug substrate CB1954
    Paul R Race
    School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
    J Mol Biol 368:481-92. 2007
    ....
  41. ncbi Biochemical characterization of trinitrotoluene transforming oxygen-insensitive nitroreductases from Clostridium acetobutylicum ATCC 824
    Razia Kutty
    Department of Biochemistry and Cell Biology MS 140, Rice University, Houston, TX 77005 1892, USA
    Arch Microbiol 184:158-67. 2005
    The genes that encode oxygen-insensitive nitroreductases from Clostridium acetobutylicum possessing 2,4,6-Trinitrotoluene (TNT) transformation activity were cloned, sequenced and characterized...
  42. ncbi The structure of Escherichia coli nitroreductase complexed with nicotinic acid: three crystal forms at 1.7 A, 1.8 A and 2.4 A resolution
    A L Lovering
    School of Biosciences, University of Birmingham, UK
    J Mol Biol 309:203-13. 2001
    ..Analysis of the structure explains the broad substrate specificity of the enzyme, and provides the basis for rational design of novel prodrugs and for site-directed mutagenesis for improved enzyme activity...
  43. ncbi Quantitative structure-activity relationships in two-electron reduction of nitroaromatic compounds by Enterobacter cloacae NAD(P)H:nitroreductase
    H Nivinskas
    Institute of Biochemistry, Vilnius, Lithuania
    Arch Biochem Biophys 385:170-8. 2001
    ..cloacae nitroreductase depends mainly on their hydride accepting properties, but not on their particular structure, and does not exclude the possibility of multistep hydride transfer...
  44. ncbi Evaluation of nitroreductase and acetyltransferase participation in N-nitrosodiethylamine genotoxicity
    Claudia Alessandra Fortes Aiub
    Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Brazil
    Chem Biol Interact 161:146-54. 2006
    ..b>Nitroreductases from bacteria seem to have a wide spectrum of substrates, as observed by the reduction of several ..
  45. pmc Roles of FrxA and RdxA nitroreductases of Helicobacter pylori in susceptibility and resistance to metronidazole
    J Y Jeong
    Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
    J Bacteriol 183:5155-62. 2001
    ..pylori strains differ in regulation of nitroreductase gene expression. We suggest that such regulatory differences may be significant functionally during human infection...
  46. ncbi Quantitation of bystander effects in nitroreductase suicide gene therapy using three-dimensional cell cultures
    William R Wilson
    Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    Cancer Res 62:1425-32. 2002
    ..This study demonstrates the utility of the multilayer tissue culture model for quantifying and optimizing bystander effects in tumors and identifies a new lead prodrug for NTR gene-dependent enzyme-prodrug therapy...
  47. ncbi Clostridia in cancer therapy
    Nigel P Minton
    Institute of Infections, Immunity and Inflammation, School of Pharmacy, University of Nottingham, Floor C, West Block, Queens Medical Centre, Nottingham NG7 2UH, UK
    Nat Rev Microbiol 1:237-42. 2003
    ....
  48. ncbi Biological and structural characterization of the Mycobacterium smegmatis nitroreductase NfnB, and its role in benzothiazinone resistance
    Giulia Manina
    Dipartimento di Genetica e Microbiologia, Universita degli Studi di Pavia, Via Ferrata, 1, 27100 Pavia, Italy
    Mol Microbiol 77:1172-85. 2010
    ..Although Mycobacterium tuberculosis seems to lack nitroreductases able to inactivate these drugs, our findings are valuable for the design of new BTZ molecules, which may be ..
  49. ncbi Frame-shift mutations in NAD(P)H flavin oxidoreductase encoding gene (frxA) from metronidazole resistant Helicobacter pylori ATCC43504 and its involvement in metronidazole resistance
    D H Kwon
    Department of Medicine and Division of Molecular Virology of Baylor College of Medicine and Veterans Affairs Medical Center, RM 3A 320 111D, 2002 Holcombe Blvd, 77030, Houston, TX 77030, USA
    FEMS Microbiol Lett 188:197-202. 2000
    ..coli to metronidazole sensitive cell. These results indicate that the frxA gene may also be involved in metronidazole resistance among clinical H. pylori isolates...
  50. ncbi Generation of Escherichia coli nitroreductase mutants conferring improved cell sensitization to the prodrug CB1954
    Jane I Grove
    The University of Birmingham Cancer Research United Kingdom Institute for Cancer Studies, Edgbaston, Birmingham B15 2TT
    Cancer Res 63:5532-7. 2003
    ..Enhanced mutant NTRs such as F124K should improve the efficacy of the NTR/CB1954 combination in cancer gene therapy...
  51. ncbi The role of two putative nitroreductases, Frm2p and Hbn1p, in the oxidative stress response in Saccharomyces cerevisiae
    Iuri Marques de Oliveira
    Departamento de Biofisica Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av Bento Goncalves 9500, 91507 970 Porto Alegre, RS, Brazil
    Yeast 27:89-102. 2010
    ..These nitroreductases can be found in bacterial species and, to a lesser extent, in eukaryotes...
  52. ncbi In silico identification of a new group of specific bacterial and fungal nitroreductases-like proteins
    Iuri Marques de Oliveira
    Centro de Biotecnologia Departamento de Biofísica, Universidade Federal do Rio Grande do Sul UFRGS, Porto Alegre, RS, Brazil
    Biochem Biophys Res Commun 355:919-25. 2007
    ..The nitroreductases are found within bacterial and some eukaryotic species...
  53. ncbi Synthesis and structure-activity relationships for 2,4-dinitrobenzamide-5-mustards as prodrugs for the Escherichia coli nfsB nitroreductase in gene therapy
    Graham J Atwell
    Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 50:1197-212. 2007
    ..A bromomesylate mustard showed superior activity against WiDr tumors grown from 1:9 mixtures of NTR+ve and NTR-ve cells, indicating a strong bystander effect in vivo...
  54. ncbi Direct positive selection for improved nitroreductase variants using SOS triggering of bacteriophage lambda lytic cycle
    C P Guise
    Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK
    Gene Ther 14:690-8. 2007
    ..Carcinoma cells infected with adenovirus expressing T41Q/N71S/F124T-NTR were sensitized to CB1954 concentrations 40- to 80-fold lower than required with WT-NTR...
  55. ncbi Structural and mechanistic studies of Escherichia coli nitroreductase with the antibiotic nitrofurazone. Reversed binding orientations in different redox states of the enzyme
    Paul R Race
    School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom
    J Biol Chem 280:13256-64. 2005
    ..We propose that the charge distribution on the FMN rings, which alters upon reduction, is an important determinant of substrate binding and reactivity in flavoproteins with broad substrate specificity...
  56. ncbi E. coli nitroreductase/CB1954 gene-directed enzyme prodrug therapy: role of arylamine N-acetlytransferase 2
    D J Mitchell
    School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia
    Cancer Gene Ther 15:758-64. 2008
    ..Moreover, endogenous NAT2, which is localized predominantly in the liver and gut, may be involved in the dose-limiting hepatic toxicity and gastrointestinal side effects seen in patients treated with the higher doses of CB1954...
  57. pmc Identification of a Mycobacterium tuberculosis putative classical nitroreductase gene whose expression is coregulated with that of the acr aene within macrophages, in standing versus shaking cultures, and under low oxygen conditions
    Anjan Purkayastha
    Department of Biomedical Sciences, University of Albany School of Public Health, Albany, New York 12201 2002, USA
    Infect Immun 70:1518-29. 2002
    ..tuberculosis genes of previously unknown function that belong to an unusual superfamily of classical nitroreductases, which may have a role for bacteria within the host environment...
  58. ncbi Virus-directed enzyme prodrug therapy: intratumoral administration of a replication-deficient adenovirus encoding nitroreductase to patients with resectable liver cancer
    Daniel H Palmer
    Cancer Research UK Institute for Cancer Studies, Department of Pathology and Liver Research Laboratories, University of Birmingham, UK
    J Clin Oncol 22:1546-52. 2004
    ..In this study, we report the first clinical trial investigating the feasibility, safety, and transgene expression of a replication-defective adenovirus encoding nitroreductase (CTL102) in patients with liver tumors...
  59. pmc 2-Amino metabolites are key mediators of CB 1954 and SN 23862 bystander effects in nitroreductase GDEPT
    N A Helsby
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
    Br J Cancer 90:1084-92. 2004
    ..These results are consistent with the reported high bystander efficiency of SN 23862 as an NTR prodrug in multicellular layers and tumour xenografts...
  60. ncbi Effect of nitroreduction on the alkylating reactivity and cytotoxicity of the 2,4-dinitrobenzamide-5-aziridine CB 1954 and the corresponding nitrogen mustard SN 23862: distinct mechanisms of bioreductive activation
    Nuala A Helsby
    Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    Chem Res Toxicol 16:469-78. 2003
    ..The single-step bioactivation of 6, to amino or hydroxylamine metabolites with similar potency to 4, is a potential advantage in the use of dinitrobenzamide mustards as prodrugs for activation by nitroreductases.
  61. ncbi Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954
    G Chung-Faye
    CRC Institute of Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TA, United Kingdom
    Clin Cancer Res 7:2662-8. 2001
    ..We are now conducting a Phase I trial combining adenovirus-mediated NTR and i.v. CB1954 (24 mg/m2) in patients with primary and secondary liver tumors...
  62. ncbi Expression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954
    A H Djeha
    Cobra Therapeutics Ltd, The Science Park, University of Keele, United Kingdom
    Cancer Gene Ther 7:721-31. 2000
    ..We also demonstrate that this enzyme/prodrug combination results in antitumoral effects in vivo when only a minority of tumor cells express the enzyme, using either cells constitutively expressing NTR or ntr gene delivery in situ...
  63. ncbi Virus-directed enzyme prodrug therapy using CB1954
    J I Grove
    Cobra Therapeutics Ltd, The Science Park, Keele, Staffordshire, UK
    Anticancer Drug Des 14:461-72. 1999
    ..The efficacy of this enzyme-prodrug approach in model systems compared with other VDEPT approaches demonstrates the feasibility and future promise of this gene therapy strategy...
  64. ncbi Bioactivation of dinitrobenzamide mustards by an E. coli B nitroreductase
    G M Anlezark
    Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wilts, U K
    Biochem Pharmacol 50:609-18. 1995
    ..This study elucidates some of the structural requirements of the enzyme and aids identification of further directions in the search for suitable prodrugs for an ADEPT nitroreductase system...
  65. ncbi Structure and site-directed mutagenesis of a flavoprotein from Escherichia coli that reduces nitrocompounds: alteration of pyridine nucleotide binding by a single amino acid substitution
    T Kobori
    Departments of Applied Biological Chemistry and Biotechnology, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
    J Biol Chem 276:2816-23. 2001
    ..The R203A mutant results in a 33-fold increase in the K(m) value for NADPH indicating that the side chain of Arg(203) plays a key role in binding NADPH possibly to interact with the 2'-phosphate group...
  66. ncbi Combined adenovirus-mediated nitroreductase gene delivery and CB1954 treatment: a well-tolerated therapy for established solid tumors
    A H Djeha
    Cobra Therapeutics Ltd, The Science Park, Keele, Staffordshire, ST5 5SP, United Kingdom
    Mol Ther 3:233-40. 2001
    ..Preexisting anti-Ad5 neutralizing antibodies may therefore be an advantage rather than an issue in the clinical use of this new therapy...
  67. pmc Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase
    S Zenno
    Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Bunkyo ku, Japan
    J Bacteriol 178:4508-14. 1996
    ..Although no appreciable sequence similarity was detected between two E. coli nitroreductases, NfsA and NfsB, NfsA exhibited a low level of the flavin reductase activity and a broad electron acceptor ..
  68. ncbi Bacillus amyloliquefaciens orthologue of Bacillus subtilis ywrO encodes a nitroreductase enzyme which activates the prodrug CB 1954
    Gill M Anlezark
    Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire SP4 0JG, UK
    Microbiology 148:297-306. 2002
    ..amyloliquefaciens YwrO, with distinct properties which will aid the rational selection of appropriate genes for applications in directed enzyme prodrug therapy (DEPT)...
  69. ncbi Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain
    W Cui
    Division of Gene Expression and Development, Roslin Institute, Roslin, Midlothian, UK
    Glia 34:272-82. 2001
    ..These results provide the first evidence that astrocytes are important for the survival of neurons in the adult brain in vivo...
  70. ncbi Potential involvement of several nitroreductases in metronidazole resistance in Helicobacter pylori
    M A Jorgensen
    School of Microbiology and Immunology, The University of New South Wales, Sydney, NSW 2052, Australia
    Arch Biochem Biophys 392:180-91. 2001
    ..The results confirmed the presence of rdxA null mutations in resistant strains and suggested that other factors involved in the metabolism of metronidazole contributed to the resistant phenotype...
  71. ncbi Purification and characterization of NfrA1, a Bacillus subtilis nitro/flavin reductase capable of interacting with the bacterial luciferase
    S Zenno
    Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Japan
    Biosci Biotechnol Biochem 62:1978-87. 1998
    ....
  72. ncbi The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)--II. A comparison of an Escherichia coli nitroreductase and Walker DT diaphorase
    R J Knox
    Molecular Pharmacology Unit, Institute of Cancer Research, Sutton, Surrey, U K
    Biochem Pharmacol 44:2297-301. 1992
    ..coli nitroreductase or Walker DT diaphorase reduced the drug. It is proposed that E. coli B nitroreductase would be a suitable enzyme for antibody-directed enzyme prodrug therapy (ADEPT) in combination with CB1954...
  73. pmc Oxygen-insensitive nitroreductases: analysis of the roles of nfsA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli
    J Whiteway
    Biology Department, Carleton University, Ottawa, Ontario, Canada K1S 5B6
    J Bacteriol 180:5529-39. 1998
    ..compounds is believed to result primarily from mutations in genes encoding oxygen-insensitive nitroreductases. We have characterized the nfsA and nfsB genes of a large number of nitrofuran-resistant mutants of ..
  74. ncbi The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)--I. Purification and properties of a nitroreductase enzyme from Escherichia coli--a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT)
    G M Anlezark
    Division of Biotechnology, PHLS Centre for Applied Microbiology and Research, Salisbury, Wiltshire, U K
    Biochem Pharmacol 44:2289-95. 1992
    ..The nitroreductase is a more active enzyme against CB1954 (kcat = 360 min-1) than Walker DT diaphorase (kcat = 4 min-1) and also has a lower Km for NADH (6 vs 75 microM)...
  75. ncbi Sensitization of colorectal and pancreatic cancer cell lines to the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) by retroviral transduction and expression of the E. coli nitroreductase gene
    N K Green
    Department of Surgery, University of Birmingham, UK
    Cancer Gene Ther 4:229-38. 1997
    ....
  76. ncbi The nitroreductase enzyme in Walker cells that activates 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) to 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide is a form of NAD(P)H dehydrogenase (quinone) (EC 1.6.99.2)
    R J Knox
    Molecular Pharmacology Unit, Institute of Cancer Research, Sutton, Surrey, U K
    Biochem Pharmacol 37:4671-7. 1988
    ..This observation could explain the reported antagonistic action of the aminoimidazole carboxamides to the antitumour effects of CB 1954...
  77. ncbi The nitroreductase prodrug SN 28343 enhances the potency of systemically administered armed oncolytic adenovirus ONYX-411(NTR)
    D C Singleton
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
    Cancer Gene Ther 14:953-67. 2007
    ..However, subsequent administration of SN 28343 resulted in the majority of mice (62.5%) being tumor-free on day 120...
  78. ncbi Towards gene therapy in prosthesis loosening: efficient killing of interface cells by gene-directed enzyme prodrug therapy with nitroreductase and the prodrug CB1954
    Jolanda J de Poorter
    Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands
    J Gene Med 7:1421-8. 2005
    ..In the current study we investigated whether interface cells can be transduced by an HAdV-5 vector carrying the E.coli-derived nitroreductase gene and sensitized to the prodrug CB1954...
  79. ncbi The rdxA gene plays a more major role than frxA gene mutation in high-level metronidazole resistance of Helicobacter pylori in Taiwan
    Yao Jong Yang
    Department of Pediatrics, Medical College, National Cheng Kung University, Tainan, Taiwan
    Helicobacter 9:400-7. 2004
    ..pylori associating with mutations of rdxA or frxA is still a debated topic. This study investigates whether rdxA and frxA mutations of H. pylori accounted for the high MIC value (>/= 64 micro g/ml) of metronidazole (Mtz)...
  80. ncbi Escherichia coli nitroreductase plus CB1954 enhances the effect of radiotherapy in vitro and in vivo
    C L White
    Targeted Therapy Laboratory, Cancer Research UK Centre for Cell and Molecular Biology, Chester Beatty Laboratories, The Institute of Cancer Research, London, UK
    Gene Ther 15:424-33. 2008
    ..Finally, adenoviral delivery of NTR plus CB1954 enhanced the effect of fractionated radiotherapy (12 Gy in four fractions) in SW480 xenograft tumours in nude mice...
  81. ncbi Selective ablation of human cancer cells by telomerase-specific adenoviral suicide gene therapy vectors expressing bacterial nitroreductase
    Alan E Bilsland
    Cancer Research UK Department of Medical Oncology, University of Glascow, Cancer Research UK Beatson Laboratories, Bearsden, UK
    Oncogene 22:370-80. 2003
    ..Finally, an efficacious effect was observed in cervical and ovarian xenograft models following single intratumoural injection with low doses of vector, followed by injection with CB1954...
  82. ncbi Nitroreductase-based therapy of prostate cancer, enhanced by raising expression of heat shock protein 70, acts through increased anti-tumour immunity
    Kai S Lipinski
    Immune Regulation Research Group, Department of Biochemistry, Trinity College, Dublin, Ireland
    Cancer Immunol Immunother 55:347-54. 2006
    ..Protection was CD4+ and CD8+ T cell-dependent and was associated with tumour-specific CTL, IFNgamma and IL-5 responses. The use of such a cytotoxic and immunomodulatory gene combination in cancer therapy warrants further pursuit...
  83. ncbi Aerobic 2- and 4-nitroreduction of CB 1954 by human liver
    Magdalene Huen Yin Tang
    Department of Pharmacology and Clinical Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
    Toxicology 216:129-39. 2005
    ..These studies demonstrate that human liver is capable of aerobic reductive bioactivation of CB 1954 to cytotoxic metabolites in vitro, possibly involving multiple enzymes, which may account for the clinical hepatotoxicity observed...
  84. ncbi Combining gene and immunotherapy for prostate cancer
    J G Young
    Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK
    Prostate Cancer Prostatic Dis 11:187-93. 2008
    ..The mechanism of this improved response is however likely to be non-immune based as it lacks a memory effect...
  85. ncbi Validation of nitroreductase, a prodrug-activating enzyme, mediated cell death in embryonic zebrafish (Danio rerio)
    Harshan Pisharath
    Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, USA
    Comp Med 57:241-6. 2007
    ..Neither the prodrugs themselves nor the NTR-EGFP fusion protein were toxic to the developing zebrafish embryos. Thus the NTR-CB 1954 and NTR-Met systems can be used to ablate a wide variety of cells and tissues in zebrafish embryos...
  86. ncbi Appropriate subcellular localisation of prodrug-activating enzymes has important consequences for suicide gene therapy
    R A Spooner
    CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, United Kingdom
    Int J Cancer 93:123-30. 2001
    ..These data demonstrate that the site of enzyme expression and prodrug activation is an important variable that requires consideration in suicide gene therapy approaches...
  87. ncbi Late expression of nitroreductase in an oncolytic adenovirus sensitizes colon cancer cells to the prodrug CB1954
    Alexander N Lukashev
    NCCR Molecular Oncology Program, Swiss Institute for Experimental Cancer Research ISREC, Epalinges CH 1066, Switzerland
    Hum Gene Ther 16:1473-83. 2005
    ....
  88. ncbi Delivery of the bacterial nitroreductase gene into endothelial cells prolongs the survival of tumour-bearing mice by bystander mechanisms
    Malika Benouchan
    UPRES 2360 Ciblage et imagerie fonctionnels de la progression tumorale, Bobigny, France
    Int J Oncol 28:457-62. 2006
    ....
  89. ncbi A new 4-nitrobenzyl carbonate prodrug of methyl 5-benzyl-2-hydroxy-11-methylene-6-oxo-5H-benzo[b]carbazole-1-carboxylate for potential use with nitroreductase-based gene-directed enzyme prodrug therapy (GDEPT)
    C Asche
    LEDSS, UMR CNRS 5616, Universite Joseph Fourier, Grenoble, France
    Pharmazie 61:244-5. 2006
    ..The compound is a substrate for E. coli nitroreductase...
  90. ncbi Enhanced efficacy of Escherichia coli nitroreductase/CB1954 prodrug activation gene therapy using an E1B-55K-deleted oncolytic adenovirus vector
    M J Chen
    Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK
    Gene Ther 11:1126-36. 2004
    ..Combination therapy of CRAd-NTR(PS1217H6) with CB1954 reduced tumour growth from 13.5- to 2.8-fold over 5 weeks, and extended median survival from 42 to 81 days, compared with no treatment...
  91. ncbi High-level, beta-catenin/TCF-dependent transgene expression in secondary colorectal cancer tissue
    K S Lipinski
    Cobra Therapeutics Ltd, Stephenson Building, Keele University Science Park, Keele, Staffordshire, ST5 5SP, UK
    Mol Ther 4:365-71. 2001
    ..CTP1 may form the basis for effective, targeted gene therapy of metastatic colon cancer and other tumors with deregulated beta-catenin/T cell factor...
  92. ncbi Telomerase-specific suicide gene therapy vectors expressing bacterial nitroreductase sensitize human cancer cells to the pro-drug CB1954
    J A Plumb
    CRC Department of Medical Oncology, University of Glasgow, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK
    Oncogene 20:7797-803. 2001
    ..Thus, telomerase-specific suicide gene therapy vectors expressing bacterial nitroreductase sensitize human cancer cells to the pro-drug CB1954...
  93. ncbi Antitumor immune responses mediated by adenoviral GDEPT using nitroreductase/CB1954 is enhanced by high-level coexpression of heat shock protein 70
    Hakim A Djeha
    ML Research, Keele University Science Park, Keele, Newcastle under Lyme, Staffordshire ST5 5SP, UK
    Cancer Gene Ther 12:560-71. 2005
    ..The enhancement of antitumor responses resulting from HSP70 coexpression was similar to that conferred by coexpression of GM-CSF...
  94. ncbi CB 1954: from the Walker tumor to NQO2 and VDEPT
    Richard J Knox
    Enact Pharma PLC, Porton Down Scientific Park, Salisbury, Wiltshire, UK
    Curr Pharm Des 9:2091-104. 2003
    ..NQO2 activity is substantially raised in tumor samples from colorectal and hepatoma patients (up to 14-fold). A phase I clinical trial of an NQO2 co-substrate with CB 1954 is scheduled...
  95. ncbi Nitroaryl phosphoramides as novel prodrugs for E. coli nitroreductase activation in enzyme prodrug therapy
    Longqin Hu
    Department of Pharmaceutical Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854, USA
    J Med Chem 46:4818-21. 2003
    ..This is about 100x more active and 27x more selective than CB1954 (1). The superior activity was attributed to its better substrate activity (k(cat)/K(m) 19x better than 1) and/or excellent cytotoxicity of phosphoramide mustard released...
  96. pmc Enzymes associated with reductive activation and action of nitazoxanide, nitrofurans, and metronidazole in Helicobacter pylori
    Gary Sisson
    Department of Microbiology and ImmunologyFaculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada
    Antimicrob Agents Chemother 46:2116-23. 2002
    ..Three enzymes that reduce NTZ were identified: two related NADPH nitroreductases, which also mediate susceptibility to metronidazole (MTZ) (RdxA and FrxA), and pyruvate oxidoreductase (POR)...
  97. ncbi Bystander cell killing spreading from endothelial to tumor cells in a three-dimensional multicellular nodule model after Escherichia coli nitroreductase gene delivery
    Malika Benouchan
    UPRES 2360 Ciblage et imagerie fonctionnels de la progression tumorale, Université de Médecine Paris XIII, Bobigny, France
    Biochem Biophys Res Commun 311:822-8. 2003
    ..To our knowledge, this is the first report indicating that GDEPT-based antiangiogenic targeting may be an effective approach for cancer treatment relied on the spreading of the bystander effect from endothelial to tumor cells...
  98. ncbi 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
    ....
  99. ncbi Studies on the nitroreductase prodrug-activating system. Crystal structures of complexes with the inhibitor dicoumarol and dinitrobenzamide prodrugs and of the enzyme active form
    Eric Johansson
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, United Kingdom
    J Med Chem 46:4009-20. 2003
    ..Finally, modulating substrate specificity by alteration of the structure of the enzyme rather than the prodrug might usefully focus on modifying the Phe124 residue and those surrounding it...
  100. ncbi The nitroreductase/CB1954 enzyme-prodrug system
    Nicola K Green
    Hybrid Systems Ltd, Littlemore Park, Oxford, UK
    Methods Mol Med 90:459-77. 2004
  101. ncbi Inducible ablation of adipocytes in adult transgenic mice expressing the E. coli nitroreductase gene
    R Felmer
    Department of Gene Expression and Development, Roslin Institute, Midlothian, Scotland, UK
    J Endocrinol 175:487-98. 2002
    ....

Research Grants10

  1. Assessment of Hypoxia in Malignant Gliomas Using EF5
    Sydney Evans; Fiscal Year: 2002
    ..We project that we will be able to institute clinical EF5 PET studies at PENN in patients with brain tumors in approximately 2 years, corresponding to the time that much of the data from the studies proposed herein will mature. ..
  2. Microenvironment: Imaging/Implications in Brain Tumors
    Sydney Evans; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  3. DOES HYPOXIA PREDICT RADIATION/SURGICAL TUMOR RESPONSE?
    Sydney Evans; Fiscal Year: 2005
    ..Primary endpoints of survival analyses will be metastasis in soft tissue sarcoma patients and local- regional recurrence in head and neck squamous cell carcinoma patients. ..
  4. LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE
    Daniel Stein; Fiscal Year: 2004
    ..By understanding the relationship between disease and the expression of a specific surface component, we can design vaccines that can prevent the disease in specific demographic groups. ..
  5. Evaluation of Hypoxia by EF5 Binding in Cervix Cancer
    Sydney Evans; Fiscal Year: 2003
    ..This will allow conversion of binding to tumor pO2. Further analyses will incorporate the area of tissue involved at various binding levels. Patient follow-up and statistical evaluations will be provided by the GOG. ..
  6. Function of Opa and LOS in gonococcal pathogenesis
    Daniel Stein; Fiscal Year: 2002
    ..The impact on human health is expected to be significant, because the new knowledge will likely make possible new approaches to the prevention and treatment of gonorrhea. ..
  7. Role of LOS and Opa in gonococcal host interactions
    Daniel C Stein; Fiscal Year: 2010
    ..The impact on human health is expected to be significant, because the new knowledge will likely make possible new approaches to the prevention and treatment of gonorrhea. ..
  8. INVASIVE NONCAPSULATED H. INFLUENZAE
    Arnold Smith; Fiscal Year: 2004
    ..Antigenic epitopes of the gene products operative in this mechanism can be used to produce a new H. influenzae conjugate vaccine active against invasive isolates. ..
  9. Virulence genes Haemophilus influenzae
    Arnold Smith; Fiscal Year: 2004
    ..With an understanding of the molecular mechanisms of colonization versus infection, strategies for prevention and intervention can be devised. ..