The thioredoxin system—From science to clinic

  title={The thioredoxin system—From science to clinic},
  author={Stephan Gromer and Sabine Urig and Katja Becker},
  journal={Medicinal Research Reviews},
The thioredoxin system—formed by thioredoxin reductase and its characteristic substrate thioredoxin—is an important constituent of the intracellular redox milieu. Interactions with many different metabolic pathways such as DNA‐synthesis, selenium metabolism, and the antioxidative network as well as significant species differences render this system an attractive target for chemotherapeutic approaches in many fields of medicine—ranging from infectious diseases to cancer therapy. In this review… 
The thioredoxin system and cancer therapy: a review
The features and functions of the Trx system are described and then its correlations with cancer are reviewed and the present knowledge about the TrX/TrxR inhibitors as anticancer drugs are summarized.
Metal- and Semimetal-Containing Inhibitors of Thioredoxin Reductase as Anticancer Agents
The current knowledge on metal- and semimetal-containing molecules capable of hampering mammalian TrxRs is summarized, with an emphasis on compounds reported in the last decade.
Small molecule inhibitors of mammalian thioredoxin reductase.
Thioredoxin and related molecules--from biology to health and disease.
Thioredoxin and binding proteins appear to control apoptosis or metabolic states such as carbohydrate and lipid metabolism related to diseases such as diabetes and atherosclerosis and the fundamental differences between bacterial and mammalian thiOREDoxin reductases offer new principles for treatment of infections.
Natural product based inhibitors of the thioredoxin-thioredoxin reductase system.
Spiroketal naphthodecalins are readily assembled by Barton's base mediated Ullmann binaphthyl ether coupling, Dakin reactions and hypervalent iodine spirocyclization. The core structures can be
The thioredoxin reductase/thioredoxin system: Novel redox targets for cancer therapy
Findings suggest that the TRX/TX system may represent an attractive target for development of new cancer therapeutics.
The thioredoxin system in cancer.
Selective inhibition of extracellular thioredoxin by asymmetric disulfides.
The most active compound identified had an IC(50) below 0.1 μM in cell culture and may be appropriate for in vivo use to interrogate the role of extracellular Trx in health and disease.


Properties and biological activities of thioredoxins.
The mammalian thioredoxins are a family of small redox proteins that undergo NADPH-dependent reduction by thiOREDoxin reductase and in turn reduce oxidized cysteine groups on proteins.
The thioredoxin/thioredoxin reductase redox system and control of cell growth.
It is shown that human thioredoxin has the same predicted amino acid sequence as adult T-cell-derived leukemic cell growth factor and site-directed mutagenesis of the active-site cysteines of thiOREDoxin has shown that redox activity is necessary for the stimulation of cell proliferation.
Human Placenta Thioredoxin Reductase
In its physiological, NADPH-reduced form, the enzyme is strongly inhibited by organic gold compounds that are widely used in the treatment of rheumatoid arthritis; for auranofin, the K i was 4 nm when measured in the presence of 50 μmthioredoxin.
Diaryl chalcogenides as selective inhibitors of thioredoxin reductase and potential antitumor agents.
A series of 12 organoselenium compounds and 16 organotellurium compounds are examined as inhibitors of human thioredoxin reductase and the cytotoxicity and antitumor activity of some of the compounds are investigated.
Aurothioglucose inhibits murine thioredoxin reductase activity in vivo.
Results indicate that in vivo administration of ATG results in significant and long-lasting inhibition of TR activity, which could lead to increased levels of oxidative stress in vivo, thereby increasing the virulence of several viruses including the coxsackievirus.
Characterization of the active center of thioredoxin reductase.