AQ4N: a new approach to hypoxia-activated cancer chemotherapy

Br J Cancer. 2000 Dec;83(12):1589-93. doi: 10.1054/bjoc.2000.1564.


Preclinical studies demonstrate that in vivo AQ4N enhances the anti-tumour effects of radiation and chemotherapeutic agents with a dose-modifying factor of approximately 2.0. With careful scheduling no, or very little, additional normal tissue toxicity should be observed. AQ4N is a bioreductive prodrug of a potent, stable, reduction product which binds non-covalently to DNA, facilitating antitumour activity in both hypoxic and proximate oxic tumour cells. AQ4N is clearly different in both its mechanism of action and potential bystander effect compared to previously identified bioreductive drugs. In particular AQ4N is the only bioreductive prodrug topoisomerase II inhibitor to enter clinical trials. Targeting this enzyme, which is crucial to cell division, may help sensitize tumours to repeated (fractionated) courses of radiotherapy. This is because in principle, the bioreduction product of AQ4N can inhibit the topoisomerase activity of hypoxic cells as they attempt to re-enter the cell cycle.

Publication types

  • Review

MeSH terms

  • Animals
  • Anthraquinones / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Cell Hypoxia
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms, Experimental / drug therapy
  • Prodrugs / therapeutic use*
  • Radiation-Protective Agents / therapeutic use*


  • Anthraquinones
  • Antineoplastic Agents
  • Prodrugs
  • Radiation-Protective Agents
  • AQ4N