Reductive metabolism of the dinitrobenzamide mustard anticancer prodrug PR-104 in mice

@article{Gu2010ReductiveMO,
  title={Reductive metabolism of the dinitrobenzamide mustard anticancer prodrug PR-104 in mice},
  author={Yongchuan Gu and Christopher P. Guise and Kashyap Patel and Maria R. Abbattista and Jie Shiuan Lie and Xueying Sun and Graham J. Atwell and Maruta Boyd and Adam Vorn Patterson and William R. Wilson},
  journal={Cancer Chemotherapy and Pharmacology},
  year={2010},
  volume={67},
  pages={543-555}
}
PR-104, a bioreductive prodrug in clinical trial, is a phosphate ester which is rapidly metabolized to the corresponding alcohol PR-104A. This dinitrobenzamide mustard is activated by reduction to hydroxylamine (PR-104H) and amine (PR-104M) metabolites selectively in hypoxic cells, and also independently of hypoxia by aldo-keto reductase (AKR) 1C3 in some tumors. Here, we evaluate reductive metabolism of PR-104A in mice and its significance for host toxicity. The pharmacokinetics of PR-104, PR… CONTINUE READING