The Thioredoxin System: A Promising Target for Cancer Drug Development

Chemistry. 2020 Aug 12;26(45):10175-10184. doi: 10.1002/chem.201905792. Epub 2020 Jun 15.

Abstract

The thioredoxin system is highly conserved system found in all living cells and comprises NADPH, thioredoxin, and thioredoxin reductase. This system plays a critical role in preserving a reduced intracellular environment, and its involvement in regulating a wide range of cellular functions makes it especially vital to cellular homeostasis. Its critical role is not limited to healthy cells, it is also involved in cancer development, and is overexpressed in many cancers. This makes the thioredoxin system a promising target for cancer drug development. As such, over the last decade, many inhibitors have been developed that target the thioredoxin system, most of which are small molecules targeting the thioredoxin reductase C-terminal redox center. A few inhibitors of thioredoxin have also been developed. We believe that more efforts should be invested in developing protein/peptide-based inhibitors against both thioredoxin reductase and/or thioredoxin.

Keywords: cancer; inhibition; oxidative stress; thioredoxin reductase; thioredoxin system.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Drug Development
  • Humans
  • NADP / chemistry*
  • Neoplasms / drug therapy*
  • Oxidation-Reduction
  • Thioredoxin-Disulfide Reductase / chemistry
  • Thioredoxin-Disulfide Reductase / metabolism*
  • Thioredoxins / metabolism
  • Thioredoxins / therapeutic use*

Substances

  • Antineoplastic Agents
  • Thioredoxins
  • NADP
  • Thioredoxin-Disulfide Reductase