Antitumour agents as inhibitors of tryptophan 2,3-dioxygenase.

Abstract

The involvement of tryptophan 2,3-dioxygenase (TDO) in cancer biology has recently been described, with the enzyme playing an immunomodulatory role, suppressing antitumour immune responses and promoting tumour cell survival and proliferation. This finding reinforces the need for specific inhibitors of TDO that may potentially be developed for therapeutic use. In this work we have screened ~2800 compounds from the library of the National Cancer Institute USA and identified seven potent inhibitors of TDO with inhibition constants in the nanomolar or low micromolar range. All seven have antitumour properties, killing various cancer cell lines. For comparison, the inhibition potencies of these compounds were tested against IDO and their inhibition constants are reported. Interestingly, this work reveals that NSC 36398 (dihydroquercetin, taxifolin), with an in vitro inhibition constant of ~16 μM, is the first TDO-selective inhibitor reported.

• Authors: Georgios Pantouris, Christopher G Mowat
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 443 Issue 1 Pg. 28-31 (Jan 03 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24269239 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Catechols
• Chromones
• NSC 36398
• Quercetin
• taxifolin
• Tryptophan Oxygenase

Topics

• Antineoplastic Agents (pharmacology)
• Catechols (pharmacology)
• Cell Line, Tumor
• Chromones (pharmacology)
• Humans
• Quercetin (analogs & derivatives, pharmacology)
• Tryptophan Oxygenase (antagonists & inhibitors)