NITROREDUCTASE: A PRODRUG‐ACTIVATING ENZYME FOR CANCER GENE THERAPY

1. The prodrug CB1954 (5‐(aziridin‐1‐yl)‐2,4‐dinitrobenzamide) is activated by Escherichia coli nitroreductase (NTR) to a potent DNA‐crosslinking agent.

[1]  N. James,et al.  A clinical trial of virus-directed enzyme prodrug therapy (VDEPT) using adenovirus encoded nitroreductase (ntr) and CB1954 in patients with localized prostate cancer (PCa). , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  D. Kerr,et al.  Enhanced efficacy of Escherichia coli nitroreductase/CB1954 prodrug activation gene therapy using an E1B-55K-deleted oncolytic adenovirus vector , 2004, Gene Therapy.

[3]  E. Sausville.  Genes in the service of therapeutic index: progress for virus-directed enzyme prodrug therapy. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  John Ellis,et al.  Virus-directed enzyme prodrug therapy: intratumoral administration of a replication-deficient adenovirus encoding nitroreductase to patients with resectable liver cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  S. Sastry,et al.  Nitrofuratoin-resistant mutants of Escherichia coli: Isolation and mapping , 2004, Molecular and General Genetics MGG.

[6]  P. Searle,et al.  Nitroaryl phosphoramides as novel prodrugs for E. coli nitroreductase activation in enzyme prodrug therapy. , 2003, Journal of medicinal chemistry.

[7]  S. White,et al.  Generation of Escherichia coli nitroreductase mutants conferring improved cell sensitization to the prodrug CB1954. , 2003, Cancer research.

[8]  W. Denny,et al.  Studies on the nitroreductase prodrug-activating system. Crystal structures of complexes with the inhibitor dicoumarol and dinitrobenzamide prodrugs and of the enzyme active form. , 2003, Journal of medicinal chemistry.

[9]  D. Kerr,et al.  Immune enhancement of nitroreductase‐induced cytotoxicity: Studies using a bicistronic adenovirus vector , 2003, International journal of cancer.

[10]  R. Vile,et al.  The oncolytic virotherapy treatment platform for cancer: Unique biological and biosafety points to consider , 2002, Cancer Gene Therapy.

[11]  W. Denny,et al.  Quantitation of bystander effects in nitroreductase suicide gene therapy using three-dimensional cell cultures. , 2002, Cancer research.

[12]  D. Kerr,et al.  Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[13]  S. White,et al.  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. , 2001, Journal of molecular biology.

[14]  D. Kerr,et al.  Combined adenovirus-mediated nitroreductase gene delivery and CB1954 treatment: a well-tolerated therapy for established solid tumors. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[15]  D. Kirn.  Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned? , 2001, Gene Therapy.

[16]  B. Hann,et al.  Loss of p14ARF in tumor cells facilitates replication of the adenovirus mutant dl1520 (ONYX-015) , 2000, Nature Medicine.

[17]  G. Parkinson,et al.  Crystal structure of FMN-dependent nitroreductase from Escherichia coli B: a prodrug-activating enzyme. , 2000, Journal of medicinal chemistry.

[18]  I. Tannock,et al.  A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer , 2000, Nature Medicine.

[19]  D. Kerr,et al.  Sensitisation of human carcinoma cells to the prodrug CB1954 by adenovirus vector‐mediated expression of E. coli nitroreductase , 2000, International journal of cancer.

[20]  D. Kerr,et al.  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 , 2000, Cancer Gene Therapy.

[21]  O. Wildner,et al.  Enzyme prodrug gene therapy: synergistic use of the herpes simplex virus-cellular thymidine kinase/ganciclovir system and thymidylate synthase inhibitors for the treatment of colon cancer. , 1999, Cancer research.

[22]  I. McNeish,et al.  Virus directed enzyme prodrug therapy for ovarian and pancreatic cancer using retrovirally delivered E. coli nitroreductase and CB1954 , 1998, Gene Therapy.

[23]  J. H. Kim,et al.  A novel three-pronged approach to kill cancer cells selectively: concomitant viral, double suicide gene, and radiotherapy. , 1998, Human gene therapy.

[24]  D. Kerr,et al.  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. , 1997, Cancer gene therapy.

[25]  D. Kirn,et al.  ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents , 1997, Nature Medicine.

[26]  W. Denny,et al.  Mustard prodrugs for activation by Escherichia coli nitroreductase in gene-directed enzyme prodrug therapy. , 1997, Journal of medicinal chemistry.

[27]  C. Springer,et al.  The bystander effect of the nitroreductase/CB1954 enzyme/prodrug system is due to a cell-permeable metabolite. , 1997, Human gene therapy.

[28]  L. Amzel,et al.  Molecular Basis of the Catalytic Differences among DT-diaphorase of Human, Rat, and Mouse* , 1997, The Journal of Biological Chemistry.

[29]  C. Springer,et al.  Expression of the bacterial nitroreductase enzyme in mammalian cells renders them selectively sensitive to killing by the prodrug CB1954. , 1995, European journal of cancer.

[30]  W. Denny,et al.  Bioactivation of dinitrobenzamide mustards by an E. coli B nitroreductase. , 1995, Biochemical pharmacology.

[31]  N. Minton,et al.  Physical characterisation of the Escherichia coli B gene encoding nitroreductase and its over-expression in Escherichia coli K12. , 1994, FEMS microbiology letters.

[32]  W. Stemmer.  Rapid evolution of a protein in vitro by DNA shuffling , 1994, Nature.

[33]  F. Friedlos,et al.  The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)--II. A comparison of an Escherichia coli nitroreductase and Walker DT diaphorase. , 1992, Biochemical pharmacology.

[34]  F. Friedlos,et al.  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). , 1992, Biochemical pharmacology.

[35]  J. Roberts,et al.  The differences in kinetics of rat and human DT diaphorase result in a differential sensitivity of derived cell lines to CB 1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) , 1991, Biochemical pharmacology.

[36]  F. Friedlos,et al.  A new cytotoxic, DNA interstrand crosslinking agent, 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide, is formed from 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by a nitroreductase enzyme in Walker carcinoma cells. , 1988, Biochemical pharmacology.

[37]  J. J. Roberts,et al.  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). , 1988, Biochemical pharmacology.

[38]  S. Venitt,et al.  The toxicity and mutagenicity of the anti-tumour drug 5-aziridino-2,4-dinitrobenzamide (CB1954) is greatly reduced in a nitroreductase-deficient strain of E. coli. , 1987, Mutagenesis.

[39]  A. Berk,et al.  Adenovirus proteins from both E1B reading frames are required for transformation of rodent cells by viral infection and DNA transfection. , 1987, Virology.

[40]  F. Friedlos,et al.  CB 1954 (2,4-dinitro-5-aziridinyl benzamide) becomes a DNA interstrand crosslinking agent in Walker tumour cells. , 1986, Biochemical and biophysical research communications.

[41]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[42]  D. R. McCalla,et al.  Genetics of Nitrofurazone Resistance in Escherichia coli , 1978, Journal of bacteriology.

[43]  L. M. Cobb,et al.  2,4-dinitro-5-ethyleneiminobenzamide (CB 1954): a potent and selective inhibitor of the growth of the Walker carcinoma 256. , 1969, Biochemical pharmacology.