Thioredoxin reductase (TrxR) (TrxR)

Thioredoxin reductase (TrxR) is a vital selenium-containing homodimeric flavoenzyme responsible for maintaining cellular redox homeostasis by reducing thioredoxin (Trx) in an NADPH-dependent manner (UniProt P30041). It exists in three main isoforms: cytosolic (TrxR1), mitochondrial (TrxR2), and testis-specific (TrxR3), each playing distinct roles in cellular compartments (PubMed: 18514213). TrxR plays a central role in DNA synthesis by providing reducing equivalents to ribonucleotide reductase and is essential for protecting cells against oxidative damage (PubMed: 29113884). In many malignancies, TrxR is significantly overexpressed to support rapid cell proliferation and counteract the high levels of reactive oxygen species (ROS) generated by tumor metabolism. Consequently, TrxR has emerged as a promising therapeutic target in oncology, where its inhibition leads to a lethal accumulation of ROS and the induction of apoptosis (PubMed: 24561017). Drugs such as auranofin, originally used for rheumatoid arthritis, are being repurposed or developed to target the unique selenocysteine residue in the enzyme's active site, effectively disrupting the thioredoxin system (PubChem CID 24199).

Other names

TXNRDThioredoxin-disulfide reductaseTRTRXRNADPH:oxidized-thioredoxin oxidoreductase

Inhibition of the enzyme's catalytic activity, specifically targeting the C-terminal selenocysteine residue, to disrupt the thioredoxin system, increase intracellular reactive oxygen species (ROS), and induce apoptosis (PubMed: 24561017).