Inhibition of Thioredoxin Reductase 1 (Trxr1) by Pyridine Compounds for Cancer Treatment

This technology includes the use of pyridines for anticancer treatment. A common feature of cancer cells is a high level of reactive oxygen species with a concomitant increase of two antioxidative systems to combat the toxicity: the glutathione and thioredoxin systems. Inhibiting either, or both, of these systems is a promising avenue to target cancer cells. Thioredoxin Reductase 1 (Trxr1) is an important selenoprotein in the thioredoxin antioxidative system which has been implicated as a potential anti-cancer target. The inventors have found that pyridinyl sulphone compounds may achieve highly selective inhibition of cytosolic thioredoxin reductase (Trxr1) by strongly-binding (in some cases, effectively irreversibly) without causing significant inhibition of glutathione reductase, an important protein in the gluthathione antioxidative system.