Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 62, Issue 16, Pages 7309-7321Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.8b01595
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Funding
- National Natural Science Foundation of China [81703337]
- Jiangsu Specially-Appointed Professors Program
- Six Talent Peaks Project in the Jiangsu Province of China [SWYY-069]
- State Key Laboratory of Natural Medicines [SKLNMKF201808, SKLNMKF201712]
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Thioredoxin reductase (TrxR) participates in the regulation of redox reactions in organisms. It works mainly via its substrate molecule, thioredoxin, to maintain the redox balance and regulate signal transduction, which controls cell proliferation, differentiation, death, and other important physiological processes. In recent years, increasing evidence has shown that the overactivation of TrxR is related to the development of tumors. The exploration of TrxR-targeted antitumor drugs has attracted wide attention and is expected to provide new therapies for cancer treatment. In this perspective, we highlight the specific relationship between TrxR and apoptotic signaling pathways. The cytoplasm and mitochondria both contain TrxR, resulting in the activation of apoptosis. TrxR activity influences reactive oxygen species (ROS) and further regulates the inflammatory signaling pathway. In addition, we discuss representative TrxR inhibitors with anticancer activity and analyze the challenges in developing TrxR inhibitors as anticancer drugs.
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