Restoring Tumour Selectivity of the Bioreductive Prodrug PR-104 by Developing an Analogue Resistant to Aerobic Metabolism by Human Aldo-Keto Reductase 1C3

• Main Authors: Maria R. Abbattista (Author), Amir Ashoorzadeh (Author), Christopher P. Guise (Author), Alexandra M. Mowday (Author), Rituparna Mittra (Author), Shevan Silva (Author), Kevin O. Hicks (Author), Matthew R. Bull (Author), Victoria Jackson-Patel (Author), Xiaojing Lin (Author), Gareth A. Prosser (Author), Neil K. Lambie (Author), Gabi U. Dachs (Author), David F. Ackerley (Author), Jeff B. Smaill (Author), Adam V. Patterson (Author)
• Format: Book
• Published: MDPI AG, 2021-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

PR-104 is a phosphate ester pre-prodrug that is converted in vivo to its cognate alcohol, PR-104A, a latent alkylator which forms potent cytotoxins upon bioreduction. Hypoxia selectivity results from one-electron nitro reduction of PR-104A, in which cytochrome P450 oxidoreductase (POR) plays an impo...