Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy

Authors: William C. Stafford, Xiaoxiao Peng, Maria Hägg Olofsson, Xiaonan Zhang, Diane K. Luci, Frank Leigh Lu, Qing Cheng, L. Tresaugues, Thomas S. Dexheimer, Nathan P. Coussens, Martin Augsten, Hanna-Stina Martinsson Ahlzén, Owe Orwar, Arne Östman, Sharon Stone‐Elander, David J. Maloney, Ajit Jadhav, Anton Simeonov, Stig Linder, Elias S.J. Arnér - Science Translational Medicine 2018 cited by 243

In mice, the most specific TXNRD1 inhibitor, here described as TXNRD1 inhibitor 1 (TRi-1), impaired growth and viability of human tumor xenografts and syngeneic mouse tumors while having little mitochondrial toxicity and being better tolerated than auranofin. These results display the therapeutic anticancer potential of irreversibly targeting cytosolic TXNRD1 using small molecules and present potent and selective TXNRD1 inhibitors. Given the pronounced up-regulation of TXNRD1 in several metastatic malignancies, it seems worthwhile to further explore the potential benefit of specific irreversible TXNRD1 inhibitors for anticancer therapy.