Technology Bundle ID
TAB-3604

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

Applications
Linked ID
E-281-2015-0
Lead Inventors
David Maloney (NCATS)
Co-Inventors
Ajit Jadhav (NCATS)
Anton Simeonov (NCATS)
Diane Luci (NCATS)
Nathan Coussens (NCATS)
Thomas Dexheimer (NCATS)
ICs
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.
Commercial Applications
Further clinical work may establish the identified compounds as anti-cancer agents (as single agent or in combination with other approaches).
Competitive Advantages
In principle, cancer cells may be uniquely sensitive to inhibition of Thioredoxin Reductase 1 (Trxr1) by compounds like pyridines. Targeting Trxr1 has the potential of causing fewer side effects than other anti-cancer treatments such as chemotherapy.

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