Auranofin

Auranofin is inhibitor of thioredoxin reductase (TrxR) with IC50 value of ∼ 88 nM [1].

TrxR, a ubiquitous homodimeric flavoenzyme, functions by transferring reducing equivalents from NADPH to thioredoxin. It has been suggested to play roles in diverse physiological and pathological conditions such as apoptosis, cancer, parasitoses, chronic inflammatory and autoimmune diseases, as well as neurodegenerative disorders [2].

In Helicobacter pylori (H. pylori), Auranofin completely inhibited bacterial growth at the concentration of 1.2 μM. Purified H. pylori TrxR was inhibited by Auranofin in a cell-free assay (IC50: ∼ 88 nM) [1]. In addition, in another study using murine 4T1 and EMT6 tumor cells, Auranofin potently radiosensitized tumor cells at concentrations of 3 ~ 10 μM [3].

In 4T1 tumor-bearing mice, Auranofin combined with Buthionine Sulfoximine (BSO), subcutaneously administrated at the concentrations of 3 and 25 mg/kg, respectively, enhanced tumor radioresponse, resulting in a tumor growth delay of 13 days, and thereby significantly increased the medium survival rate, while neither of these pharmaceuticals were effective when administered on their own [3].

References:

[1]. Owings J P, McNair N N, Mui Y F, et al. Auranofin and N-heterocyclic carbene gold-analogs are potent inhibitors of the bacteria Helicobacter pylori. FEMS Microbiology Letters, 2016, 363(14): 1-6.

[2]. Saccoccia F, Angelucci F, Boumis G, et al. Thioredoxin reductase and its inhibitors. Current Protein & Peptide Science, 2014, 15(6): 621-646.

[3]. Wang H, Bouzakoura S, de Mey S, et al. Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species. Oncotarget, 2017, 8(22): 35728-35742.