ArticleBritish journal of cancer2009
E. coli NfsA: an alternative nitroreductase for prodrug activation gene therapy in combination with CB1954.
Article in British journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 70 citations in OpenAlex.
- Cloning, purification and possible use of a Bacillus nitroreductase in biotechnological applications.Scientific reports · 2026Article
- Structural Evaluation of a Nitroreductase Engineered for Improved Activation of the 5-Nitroimidazole PET Probe SN33623.International journal of molecular sciences · 2024Article
- The Catalysis Mechanism ofInternational journal of molecular sciences · 2024Article
- Suicide gene strategies applied in ovarian cancer studies.Cancer gene therapy · 2023Review
- Oxygen-insensitive nitroreductase E. coli NfsA, but not NfsB, is inhibited by fumarate.Proteins · 2023Article
- The dinitrobenzamide mustard prodrugs, PR-104A and SN27686, for use in a novel MNDEPT cancer prodrug therapy approach.Bioscience reports · 2023Article
- The Crystal Structure of Engineered Nitroreductase NTR 2.0 and Impact of F70A and F108Y Substitutions on Substrate Specificity.International journal of molecular sciences · 2023Article
- The 3D-structure, kinetics and dynamics of the E. coli nitroreductase NfsA with NADPFEBS letters · 2022Article
- The structures of E. coli NfsA bound to the antibiotic nitrofurantoin; to 1,4-benzoquinone and to FMN.The Biochemical journal · 2021Article
- The YfkO Nitroreductase from Bacillus Licheniformis on Gold-Coated Superparamagnetic Nanoparticles: Towards a Novel Directed Enzyme Prodrug Therapy Approach.Pharmaceutics · 2021Article
- A Chemical Approach for Programmable Protein Outputs Based on Engineered Cell Interactions.ACS chemical biology · 2021Article
- RepurposingTheranostics · 2021Article
- Engineering theFrontiers in pharmacology · 2021Article
- Evaluation of two xenobiotic reductases from Pseudomonas putida for their suitability for magnetic nanoparticle-directed enzyme prodrug therapy as a novel approach to cancer treatment.MicrobiologyOpen · 2020Article
- Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy.Journal of functional biomaterials · 2019Article
- Enzyme/Prodrug Systems for Cancer Gene Therapy.Current pharmacology reports · 2016Article
- Heterologous Overexpression and Biochemical Characterization of a Nitroreductase from Gluconobacter oxydans 621H.Molecular biotechnology · 2016Article
- Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo.Oncotarget · 2014Article
- Article
- Selective esterase-ester pair for targeting small molecules with cellular specificity.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Prodrug activation gene therapy is a developing approach to cancer treatment, whereby prodrug-activating enzymes are expressed in tumour cells. After administration of a non-toxic prodrug, its conversion to cytotoxic metabolites directly kills tumour cells expressing the activating enzyme, whereas the local spread of activated metabolites can kill nearby cells lacking the enzyme (bystander cell killing). One promising combination that has entered clinical trials uses the nitroreductase NfsB from Escherichia coli to activate the prodrug, CB1954, to a potent bifunctional alkylating agent. NfsA, the major E. coli nitroreductase, has greater activity with nitrofuran antibiotics, but it has not been compared in the past with NfsB for the activation of CB1954. We show superior in vitro kinetics of CB1954 activation by NfsA using the NADPH cofactor, and show that the expression of NfsA in bacterial or human cells results in a 3.5- to 8-fold greater sensitivity to CB1954, relative to NfsB. Although NfsB reduces either the 2-NO(2) or 4-NO(2) positions of CB1954 in an equimolar ratio, we show that NfsA preferentially reduces the 2-NO(2) group, which leads to a greater bystander effect with cells expressing NfsA than with NfsB. NfsA is also more effective than NfsB for cell sensitisation to nitrofurans and to a selection of alternative, dinitrobenzamide mustard (DNBM) prodrugs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.