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硫氧还蛋白还原酶及其抑制剂的研究进展

吴石威, 张惠, 李乾斌, 胡高云

吴石威, 张惠, 李乾斌, 胡高云. 硫氧还蛋白还原酶及其抑制剂的研究进展[J]. 中国药科大学学报, 2016, 47(5): 511-520. DOI: 10.11665/j.issn.1000-5048.20160502
引用本文: 吴石威, 张惠, 李乾斌, 胡高云. 硫氧还蛋白还原酶及其抑制剂的研究进展[J]. 中国药科大学学报, 2016, 47(5): 511-520. DOI: 10.11665/j.issn.1000-5048.20160502
WU Shiwei, ZHANG Hui, LI Qianbin, HU Gaoyun. Advances in thioredoxin reductase and its inhibitors[J]. Journal of China Pharmaceutical University, 2016, 47(5): 511-520. DOI: 10.11665/j.issn.1000-5048.20160502
Citation: WU Shiwei, ZHANG Hui, LI Qianbin, HU Gaoyun. Advances in thioredoxin reductase and its inhibitors[J]. Journal of China Pharmaceutical University, 2016, 47(5): 511-520. DOI: 10.11665/j.issn.1000-5048.20160502

硫氧还蛋白还原酶及其抑制剂的研究进展

基金项目: 国家自然科学基金资助项目(No.21102184,No.21172268,No.81573287);国家“重大新药创制”科技重大专项资助项目(No.2012ZX09103101-025)

Advances in thioredoxin reductase and its inhibitors

  • 摘要: 硫氧还蛋白还原酶(thioredoxin reductase,TrxR)是存在于细胞中的含硒同型二聚体黄素酶,其主要功能为调节氧化还原平衡,与细胞的增殖、凋亡以及肿瘤的发生、转移、血管生成中密切相关。含硒C末端活性位点是TrxR的特有结合域,对TrxR与底物的结合具有重要作用,其靶向抑制剂正成为治疗与肿瘤相关疾病的研究热点。本文从TrxR的结构特点及其与肿瘤相关的生理功能出发,根据其与底物结合能力进行分类,将TrxR抑制剂分为可逆和不可逆两类,对两类抑制剂的最新研究进展进行了综述。
    Abstract: Thioredoxin reductase(TrxR)is a seleniferous homodimeric flavoenzyme, which is ubiquitously expressed in all cells and plays a crucial role in the redox regulation of numerous celluar signaling pathways involved in cell survival and proliferation. TrxR maintains cellular redox equilibrium. Recent researches have illuminated that TrxR overexpressed in many tumors, is closely associated with the evolution, progression and apoptosis of tumor. TrxR contains a reactive and solvent accessible selenocysteine residue which is located on a flexible C-terminal arm of the protein. This selenocysteine is essentially involved in the catalytic cycle of TrxR and thus represents an attractive binding site for inhibitors. The TrxR inhibitors as novel target-drug in cancer therapy have been extensively studied and elucidated. This article summarized the latest progress in TrxR inhibitors according to the binding capacity of TrxR and substrate.
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  • 刊出日期:  2016-10-24

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