Designing of novel ERR gamma inverse agonists by molecular modeling studies of docking and 3D-QSAR on hydroxytamoxifen derivatives

doi:10.1007/s00044-019-02402-9

	Designing of novel ERR gamma inverse agonists by molecular modeling studies of docking and 3D-QSAR on hydroxytamoxifen derivatives
	Li, Rui 1; Du, Yongli 1; Shen, Jingkang 2
刊名	MEDICINAL CHEMISTRY RESEARCH
	2019-10-01
卷号	28 期号:10 页码:1661-1673
关键词	ERR gamma inverse agonist Molecular docking 3D-QSAR CoMFA CoMSIA
ISSN号	1054-2523
DOI	10.1007/s00044-019-02402-9
通讯作者	Du, Yongli(ylduyjs@163.com)
英文摘要	ERR gamma inverse agonist is a powerful therapeutic target for the treatment of cancers and certain metabolic disorders. Until now, only GSK5814 was reported as selective ERR gamma inverse agonist. So 60 newly hydroxytamoxifen analogues were selected to perform molecular docking and 3D-QSAR study to design more selective inverse agonist of ERR gamma. Both established CoMFA and CoMSIA models obtained high predictive and satisfactory value, demonstrated that bulky, hydrophobic and negative electrostatic substitutions are preferred at R-2 position, and introducing hydrophilic and H-bond donor and acceptor groups at R-1 and R-4 positions is greatly important for improving binding activities. The obtained information will be useful to provide clues for rationally designing novel and high potency ERR gamma inverse agonists.
资助项目	National Natural Science Foundation of China[81872744] ; Shandong Natural Science Foundation of China[ZR2019MH046]
WOS关键词	INDEPENDENT TRANSCRIPTIONAL ACTIVATION ; LIGAND-BINDING DOMAIN ; RECEPTOR-GAMMA ; 4-HYDROXYTAMOXIFEN ANALOGS ; BIOLOGICAL EVALUATION ; ESTROGEN ; IDENTIFICATION ; ALPHA
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER BIRKHAUSER
WOS记录号	WOS:000485314100007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288745]
专题	中国科学院上海药物研究所
通讯作者	Du, Yongli
作者单位	1.Qilu Univ Technol, Shandong Acad Sci, Sch Chem & Pharmaceut Engn, 3501 Daxue Rd, Jinan 250353, Shandong, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Li, Rui,Du, Yongli,Shen, Jingkang. Designing of novel ERR gamma inverse agonists by molecular modeling studies of docking and 3D-QSAR on hydroxytamoxifen derivatives[J]. MEDICINAL CHEMISTRY RESEARCH,2019,28(10):1661-1673.
APA	Li, Rui,Du, Yongli,&Shen, Jingkang.(2019).Designing of novel ERR gamma inverse agonists by molecular modeling studies of docking and 3D-QSAR on hydroxytamoxifen derivatives.MEDICINAL CHEMISTRY RESEARCH,28(10),1661-1673.
MLA	Li, Rui,et al."Designing of novel ERR gamma inverse agonists by molecular modeling studies of docking and 3D-QSAR on hydroxytamoxifen derivatives".MEDICINAL CHEMISTRY RESEARCH 28.10(2019):1661-1673.