Identification of novel anti-inflammatory Nur77 modulators by virtual screening

doi:10.1016/j.bioorg.2021.104912

	Identification of novel anti-inflammatory Nur77 modulators by virtual screening
	Ding, Xiaoyu 2,5; Zhao, Zijie 2,3,4,5; Wu, Yue 2,5; Zhang, Hao 2; Chen, Kaixian 2,3,4,5; Luo, Cheng 1,2,5; Luo, Xiaomin 2,5; Xu, Heng 1,2
刊名	BIOORGANIC CHEMISTRY
	2021-07-01
卷号	112 页码:7
关键词	Nur77 Binding site evaluation Virtual Screening Inflammation
ISSN号	0045-2068
DOI	10.1016/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.
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关键词	ORPHAN NUCLEAR RECEPTOR ; CANCER-CELLS ; EXPRESSION ; INDUCTION ; TR3 ; CHEMOTHERAPY ; ACTIVATION ; TARGET ; DEATH ; NR4A1
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000661870300007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297167]
专题	中国科学院上海药物研究所
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.