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Identification of novel anti-inflammatory Nur77 modulators by virtual screening

文献类型：期刊论文

作者Ding, Xiaoyu2,5; Zhao, Zijie2,3,4,5; Wu, Yue2,5; Zhang, Hao2; Chen, Kaixian2,3,4,5; Luo, Cheng1,2,5; Luo, Xiaomin2,5; Xu, Heng1,2
刊名BIOORGANIC CHEMISTRY
出版日期2021-07-01
卷号112页码:7
关键词Nur77 Binding site evaluation Virtual Screening Inflammation
ISSN号0045-2068
DOI10.1016/j.bioorg.2021.104912
通讯作者Luo, Cheng(cluo@simm.ac.cn) ; Luo, Xiaomin(xmluo@simm.ac.cn) ; Xu, Heng(idaheng@simm.ac.cn)
英文摘要Orphan nuclear receptor Nur77 is a unique member of the NR4A nuclear receptor subfamily, which is critical for cellular processes especially the inflammatory responses. Many efforts have been made to discover novel scaffold small molecules targeting Nur77. Herein, we evaluated the previously reported binding sites in crystal structures of Nur77 with small molecules, and then discovered compound 13 as a hit of Nur77 via virtual screening targeting the best-scored binding site. Based on the results of fluorescence titration assay, structure & ndash;activity relationship (SAR) analysis was summarized for compound 13 and its analogs. Among these analogs, compound 13e displayed the most potent binding affinity (0.54 +/- 0.02 mu M). The binding mode of compound 13e was predicted via molecule docking. Moreover, 13e exhibited significant anti-inflammation activity in TNF-alpha induced HepG2 cell model. Taken together, these results provided a new insight into the understanding the functions of specific binding sites on Nur77 for small molecular compounds, and the development of new scaffold Nur77 modulators.
WOS关键词ORPHAN NUCLEAR RECEPTOR ; CANCER-CELLS ; EXPRESSION ; INDUCTION ; TR3 ; CHEMOTHERAPY ; ACTIVATION ; TARGET ; DEATH ; NR4A1
资助项目China Postdoctoral Science Foundation[2020M681430] ; China Postdoctoral Science Foundation[2019M661673] ; National Natural Science Foundation of China[91853205] ; National Natural Science Foundation of China[81625022] ; National Natural Science Foundation of China[81903538] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Programof China[2018ZX09711002-001-003]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000661870300007
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/297167]  
专题新药研究国家重点实验室
通讯作者Luo, Cheng; Luo, Xiaomin; Xu, Heng
作者单位1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310000, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 200031, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
5.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Ding, Xiaoyu,Zhao, Zijie,Wu, Yue,et al. Identification of novel anti-inflammatory Nur77 modulators by virtual screening[J]. BIOORGANIC CHEMISTRY,2021,112:7.
APA Ding, Xiaoyu.,Zhao, Zijie.,Wu, Yue.,Zhang, Hao.,Chen, Kaixian.,...&Xu, Heng.(2021).Identification of novel anti-inflammatory Nur77 modulators by virtual screening.BIOORGANIC CHEMISTRY,112,7.
MLA Ding, Xiaoyu,et al."Identification of novel anti-inflammatory Nur77 modulators by virtual screening".BIOORGANIC CHEMISTRY 112(2021):7.

入库方式： OAI收割

来源：上海药物研究所

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