Nitroreductase: a prodrug-activating enzyme for cancer gene therapy.

Journal article

1. The prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) is activated by Escherichia coli nitroreductase (NTR) to a potent DNA-crosslinking agent. 2. Virus-mediated expression of NTR in tumour cells sensitizes them to CB1954 in vitro and in vivo, providing the basis for a strategy of cancer gene therapy. 3. A phase I trial of CB1954 in cancer patients has been completed, documenting the pharmacokinetics and establishing an acceptable dose. Subsequent trials of the replication-defective ...

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Authors: Searle, P; Chen, M; Hu, L; Race, P; Lovering, A

• Journal: Clinical and experimental pharmacology and physiology
• Volume: 31
• Issue: 11
• Pages: 811-816
• Publication date: 2004-11-01
• DOI: 10.1111/j.1440-1681.2004.04085.x
• EISSN: 1440-1681
• ISSN: 0305-1870
• Language: English
• Keywords: Genetic Therapy; Animals; Aziridines; Prodrugs; Nitroreductases; Genetic Engineering; Biotransformation; Humans; Combined Modality Therapy; Antineoplastic Agents; Neoplasms; Clinical Trials as Topic