Small molecule inhibitors of mammalian thioredoxin reductase

Mammalian thioredoxin reductases (TrxRs) are a family of NADPH-dependent flavoproteins with a penultimate selenocysteine residue at the carboxy-terminus. Besides their native substrate thioredoxins (Trx), the enzymes show a broad substrate specificity, at least partially, because of the C-terminal r...

Full description

Saved in:
Bibliographic Details
Published in:Free radical biology & medicine 2012-01, Vol.52 (2), p.257-265
Main Authors: Cai, Wenqing, Zhang, Liangwei, Song, Yanlin, Wang, Baolin, Zhang, Baoxin, Cui, Xuemei, Hu, Guanming, Liu, Yaping, Wu, Jincai, Fang, Jianguo
Format: Article
Language:English
Subjects:
Animals
anticarcinogenic activity
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cancer
chemotherapy
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Enzyme Inhibitors - therapeutic use
enzymes
flavoproteins
Humans
Inhibitory Concentration 50
mammals
Molecular Structure
Neoplasms - drug therapy
Neoplasms - enzymology
Redox
Selenocysteine
substrate specificity
Thioredoxin
Thioredoxin-Disulfide Reductase - antagonists & inhibitors
Thioredoxin-Disulfide Reductase - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mammalian thioredoxin reductases (TrxRs) are a family of NADPH-dependent flavoproteins with a penultimate selenocysteine residue at the carboxy-terminus. Besides their native substrate thioredoxins (Trx), the enzymes show a broad substrate specificity, at least partially, because of the C-terminal redox-active site that is easily accessible in the reduced form. TrxRs are ubiquitous in all kinds of cells and have a critical role in regulating intracellular redox signaling. In recent years, a wealth of evidence has revealed that overactivation/dysfunction of TrxRs is closely related to various diseases, especially in tumor development, and thus the past decades have witnessed an expanding interest in finding TrxRs inhibitors, which might be promising agents for cancer chemotherapy. Herein we reviewed the small molecule inhibitors of mammalian TrxRs, with an emphasis on those that have potential anticancer activity. This review includes the nonpatent references up to 2010 that deal with mammalian TrxR inhibitors. ► A full review of small molecule inhibitors of mammalian thioredoxin reductase. ► Over 200 chemical structures illustrated. ► Inhibitors with potential anticancer activity further discussed.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2011.10.447