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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Nitroaryl phosphoramides as novel prodrugs for E. coli nitroreductase activation in enzyme prodrug therapy.

Cyclic and acyclic nitroaryl phosphoramide mustard analogues were activated by E. coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4-nitrobenzyl phosphoramide mustard (7) showed 167 500x selective cytotoxicity toward nitroreductase-expressing V79 cells with an IC(50) as low as 0.4 nM. 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.[1]

References

  1. Nitroaryl phosphoramides as novel prodrugs for E. coli nitroreductase activation in enzyme prodrug therapy. Hu, L., Yu, C., Jiang, Y., Han, J., Li, Z., Browne, P., Race, P.R., Knox, R.J., Searle, P.F., Hyde, E.I. J. Med. Chem. (2003) [Pubmed]
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