Unravelling the anti-cancer mechanisms elicited by non-covalent thioredoxin reductase inhibitors for triple negative breast cancer therapy.

ABSTRACT: Thioredoxin reductases (cytosolic TXNRD1 and mitochondrial TXNRD2) are antioxidant enzymes often overexpressed in tumors, including triple negative breast cancer (TNBC), making them promising targets for cancer therapy. Inhibiting these enzymes may worsen the already elevated oxidative stress in cancer cells, ultimately leading to cell death through a pro-oxidant mechanism. However, selectively targeting TXNRDs has been challenging due to the traditional reliance on covalent inhibition strategies. Recent studies have identified a druggable allosteric pocket in this enzyme family, paving the way for the development of novel non-covalent inhibitors, referred to as TXNRD(i)s. These inhibitors have been tested in TNBC models and have demonstrated a range of anti-cancer effects. To understand t

SUBMITTER: Rullo A 

PROVIDER: S-EPMC12816872 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature