Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects

J Med Chem. 2017 Sep 28;60(18):7617-7635. doi: 10.1021/acs.jmedchem.6b01672. Epub 2017 May 23.


The increasing understanding of the role of nitric oxide (NO) in cancer biology has generated significant progress in the use of NO donor-based therapy to fight cancer. These advances strongly suggest the potential adoption of NO donor-based therapy in clinical practice, and this has been supported by several clinical studies in the past decade. In this review, we first highlight several types of important NO donors, including recently developed NO donors bearing a dinitroazetidine skeleton, represented by RRx-001, with potential utility in cancer therapy. Special emphasis is then given to the combination of NO donor(s) with other therapies to achieve synergy and to the hybridization of NO donor(s) with an anticancer drug/agent/fragment to enhance the activity or specificity or to reduce toxicity. In addition, we briefly describe inducible NO synthase gene therapy and nanotechnology, which have recently entered the field of NO donor therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Azetidines / chemistry
  • Azetidines / pharmacology
  • Azetidines / therapeutic use*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Donors / therapeutic use*
  • Nitric Oxide Synthase / metabolism
  • Nitro Compounds / chemistry
  • Nitro Compounds / pharmacology
  • Nitro Compounds / therapeutic use*


  • Antineoplastic Agents
  • Azetidines
  • Nitric Oxide Donors
  • Nitro Compounds
  • RRx-001
  • Nitric Oxide
  • Nitric Oxide Synthase