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, Zijie2,3,4,5 ; Wu, Yue 2,5; Zhang, Hao 2; Chen, Kaixian2,3,4,5 ; Luo, Cheng 1,2,5; Luo, Xiaomin 2,5; Xu, Heng 1,2
	2021-07
发表期刊	BIOORGANIC CHEMISTRY (IF:4.5[JCR-2023],4.7[5-Year])
ISSN	0045-2068
EISSN	1090-2120
卷号	112
DOI	10.1016/j.bioorg.2021.104912
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.
关键词	Nur77 Binding site evaluation Virtual Screening Inflammation
收录类别	SCIE ; IC
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Organic
WOS记录号	WOS:000661870300007
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127563
专题	生命科学与技术学院_硕士生免疫化学研究所生命科学与技术学院_特聘教授组_陈凯先组
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.
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.
MLA	Ding, Xiaoyu,et al."Identification of novel anti-inflammatory Nur77 modulators by virtual screening".BIOORGANIC CHEMISTRY 112(2021).