Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: A phase I and pharmacokinetic study of its prodrug, CB1954

Clinical Cancer Research

Volumn 7, Issue 9, 2001, Pages 2662-2668

  Chung Faye, Guy ^a   Palmer, Daniel ^a   Anderson, David ^a   Clark, Joanna ^a   Dowries, Mandy ^a   Baddeley, Joanna ^a   Hussain, Syed ^a   Murray, Philip I ^a   Searle, Peter ^a   Seymour, Leonard ^a   Ferry, David ^a   Kerr, David J ^a   Harris, Peter A ^b  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b KEELE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 (1 AZIRIDINYL) 2,4 DINITROBENZAMIDE; DRUG METABOLITE; NITROIMIDAZOLE; OXIDOREDUCTASE; PRODRUG;

ABDOMINAL PAIN; ADENOVIRUS; ADULT; AGED; ALOPECIA; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; BONE MARROW SUPPRESSION; CLINICAL ARTICLE; CLINICAL TRIAL; DIARRHEA; DIGESTIVE SYSTEM CANCER; DOSE RESPONSE; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG METABOLISM; DRUG STRUCTURE; DRUG TOLERABILITY; EXPRESSION VECTOR; FATIGUE; FEMALE; HUMAN; IC 50; LIVER TOXICITY; MALE; NAUSEA AND VOMITING; NEPHROTOXICITY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; URINARY EXCRETION;

ABDOMINAL PAIN; ADENOVIRIDAE; ADULT; AGED; ANOREXIA; ANTINEOPLASTIC AGENTS; AZIRIDINES; DIARRHEA; DOSE-RESPONSE RELATIONSHIP, DRUG; FATIGUE; FEMALE; GASTROINTESTINAL NEOPLASMS; GENETIC VECTORS; HUMANS; INJECTIONS, INTRAPERITONEAL; INJECTIONS, INTRAVENOUS; MALE; MIDDLE AGED; NAUSEA; NITROREDUCTASES; PRODRUGS; TREATMENT OUTCOME; VOMITING;

EID: 0034814342     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (18)

1. 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
2. Sensitization of colorectal and pancreatic cancer cell lines to the prodrug 5-(aziridin-1-yl)-2, 4-dinitrobenzamide (CB 1954) by retroviral transduction and expression of the E. coli nitroreductase gene
3. Sensitization of human carcinoma cells to the prodrug CB1954 by adenovirus vector-mediated expression of E. coli nitroreductase
4. Expression of the bacterial nitroreductase enzyme in mammalian cells renders them selectively sensitive to killing by the prodrug CB1954
5. Virus directed enzyme prodrug therapy for ovarian and pancreatic cancer using retrovirally delivered E. coli nitroreductase and CB1954
6. 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)
7. The bioactivation of 5-(aziridin-1-y1)-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)
8. 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)
9. The bystander effect of the nitroreductase/CB1954 enzyme/prodrug system is due to a cell-permeable metabolite
10. 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
11. Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier solution
12. High-performance liquid chromatographic method for sensitive determination of the alkylating agent CB1954 in human plasma
13. CB 1954 revisited. I. Disposition kinetics and metabolism
14. CB 1954 (2, 4-dinitro-5-aziridinyl benzamide) becomes a DNA interstrand crosslinking agent in Walker tumor cells
15. The properties of total adducts and interstrand crosslinks in the DNA of cells treated with CB 1954. Exceptional frequency and stability of the crosslink
16. The effect of monofunctional or difunctional platinum adducts and of various other associated DNA damage on the expression of transfected DNA in mammalian cell lines sensitive or resistant to difunctional agents
17. Nitroreductase-mediated cell ablation is very rapid and mediated by a p53-independent apoptotic pathway