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Thimerosal, a competitive thioredoxin reductase 1 (TrxR1) inhibitor discovered via high-throughput screening

文献类型：期刊论文

作者Ni, Yicheng1,2; Luo, Zhongyuan2; Lv, Yixin1; Ma, Shuyuan1,2; Luo, Cheng1,2; Du, Daohai2
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
出版日期2023-04-02
卷号650页码:117-122
关键词Thioredoxin reductase 1 inhibitor Chemical probe High -throughput screening Thimerosal
ISSN号0006-291X
DOI10.1016/j.bbrc.2023.02.014
通讯作者Luo, Cheng() ; Du, Daohai(dhdu@simm.ac.cn)
英文摘要Thioredoxin reductase 1 (TrxR1) is considered as an important anti-cancer drug target, inhibition of which can induce reactive oxygen species (ROS)-mediated apoptosis of human cancer cells. Here, we developed and optimized a high-throughput screening (HTS) assay based on enzyme kinetics for the discovery of TrxR1 inhibitors. By utilizing this assay, we performed a HTS for 2500 compounds from an in-house library against TrxR1. We found that a vaccine preservative, thimerosal, strongly inhibited TrxR1 in a competitive and reversible manner with an IC50 of 24.08 +/- 0.86 nM. In addition, we determined that thiomersal has an inhibitory effect on the proliferation of A549 lung cancer cell line, with a GI50 of 6.81 +/- 0.09 mM, slightly more potent than auranofin (GI50 1/4 11.85 +/- 0.56 mM). Furthermore, we showed by flow cytometer that thimerosal effectively increased the content of ROS in A549 cells. Therefore, our work provided a high-throughput screening assay to quickly and effectively discover TrxR1 inhibitors, identifying thiomersal as a novel TrxR1 inhibitor and chemical probe. (c) 2023 Elsevier Inc. All rights reserved.
WOS关键词SMALL-MOLECULE INHIBITORS ; EXPRESSION ; SYSTEM ; GROWTH
资助项目National Centre for Protein Science Shanghai (Protein Expression and Purification system) ; National Key Research and Development Program of China[2021ZD0203900] ; National Natural Science Foundation of China[91853205] ; National Natural Science Foundation of China[81821005]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics
语种英语
WOS记录号WOS:000992870500001
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/306605]  
专题新药研究国家重点实验室
通讯作者Luo, Cheng; Du, Daohai
作者单位1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Ctr Chem Biol,State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Ni, Yicheng,Luo, Zhongyuan,Lv, Yixin,et al. Thimerosal, a competitive thioredoxin reductase 1 (TrxR1) inhibitor discovered via high-throughput screening[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2023,650:117-122.
APA Ni, Yicheng,Luo, Zhongyuan,Lv, Yixin,Ma, Shuyuan,Luo, Cheng,&Du, Daohai.(2023).Thimerosal, a competitive thioredoxin reductase 1 (TrxR1) inhibitor discovered via high-throughput screening.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,650,117-122.
MLA Ni, Yicheng,et al."Thimerosal, a competitive thioredoxin reductase 1 (TrxR1) inhibitor discovered via high-throughput screening".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 650(2023):117-122.

入库方式： OAI收割

来源：上海药物研究所

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