Molecular mechanisms and clinical implications of the gold drug auranofin

Auranofin (AUR) is an orally available lipophilic gold-based anti-inflammatory compound used for the treatment of rheumatoid arthritis (RA). Recent evidence indicates that AUR may have a diverse range of biological properties, including antibacterial, antiviral, antifungal, antiparasitic, and anticancer activities. Therefore, considerable attention has turned to the repurposing AUR in order to expand its clinical applications. AUR inhibits the enzymatic activity of thioredoxin reductase (TrxR); thus, the principal function of AUR is to regulate cellular redox homeostasis. The mechanisms proposed for AUR focus mainly on its inhibitory effects on antioxidant defensive systems, the ubiquitin proteasome machinery, and signaling pathways related to cell proliferation, apoptosis, and ferroptosis. Moreover, advanced techniques to determine its stereospecific chemistry led to the identification of a variety of targets for AUR, and this increased knowledge regarding AUR will likely facilitate its use in new clinical indications. Here, we provide an overview of AUR's diverse range of biological activities, its underlying mechanisms, and its potential use in the treatment of a wide spectrum of diseases.