The discovery of a novel series of potential ERR alpha inverse agonists based on p-nitrobenzenesulfonamide template for triple-negative breast cancer in vivo

doi:10.1080/14756366.2021.1995728

	The discovery of a novel series of potential ERR alpha inverse agonists based on p-nitrobenzenesulfonamide template for triple-negative breast cancer in vivo
	Gao, Zhipei 1; Wang, Tianxiao 2; Li, Rui 1; Du, Yongli 1; Lv, Han 1; Zhang, Liudi 2; Chen, Haifei 2; Shi, Xiaojin 2; Li, Qunyi 2; Shen, Jingkang 3
刊名	JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
	2022
卷号	37 期号:1 页码:125-134
关键词	ERR alpha TNBC p-Nitrobenzenesulfonamide inverse agonist
ISSN号	1475-6366
DOI	10.1080/14756366.2021.1995728
通讯作者	Du, Yongli(ylduyjs2019@163.com) ; Li, Qunyi(qyli1234@163.com)
英文摘要	Oestrogen related receptor alpha participated in the regulation of oxidative metabolism and mitochondrial biogenesis, and was overexpressed in many cancers including triple-negative breast cancer. A set of new ERR alpha inverse agonists based on p-nitrobenzenesulfonamide template were discovered and compound 11 with high potent activity (IC50 = 0.80 mu M) could significantly inhibit the transcription of ERR alpha-regulated target genes. By regulating the downstream signalling pathway, compound 11 could suppress the migration and invasion of the ER-negative MDA-MB-231 cell line. Furthermore, compound 11 demonstrated a significant growth suppression of breast cancer xenograft tumours in vivo (inhibition rate 23.58%). The docking results showed that compound 11 could form hydrogen bonds with Glu331 and Arg372 in addition to its hydrophobic interaction with ligand-binding domain. Our data implied that compound 11 represented a novel and effective ERR alpha inverse agonist, which had broad application prospects in the treatment of triple-negative breast cancer.
资助项目	National Natural Science Foundation of China[81872744] ; National Natural Science Foundation of China[81973399] ; National Natural Science Foundation of China[81901399] ; Shandong Provincial Natural Science Foundation[ZR2019MH046] ; Shanghai Health Commission Youth Fund Projects[20184Y0194] ; Shanghai Health Commission Youth Fund Projects[20204Y0445]
WOS关键词	ESTROGEN-RELATED RECEPTOR ; CRYSTAL-STRUCTURE ; SURVIVAL ; IDENTIFICATION ; EXPRESSION ; COMPLEX ; GROWTH ; CELLS
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种	英语
出版者	TAYLOR & FRANCIS LTD
WOS记录号	WOS:000729295100001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299223]
专题	中国科学院上海药物研究所
通讯作者	Du, Yongli; Li, Qunyi
作者单位	1.Qilu Univ Technol, Sch Chem & Chem Engn, Shandong Acad Sci, 3501 Da Xue Rd, Jinan 250353, Peoples R China 2.Fudan Univ, Huashan Hosp, Dept Pharm, Shanghai 200040, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Gao, Zhipei,Wang, Tianxiao,Li, Rui,et al. The discovery of a novel series of potential ERR alpha inverse agonists based on p-nitrobenzenesulfonamide template for triple-negative breast cancer in vivo[J]. JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY,2022,37(1):125-134.
APA	Gao, Zhipei.,Wang, Tianxiao.,Li, Rui.,Du, Yongli.,Lv, Han.,...&Shen, Jingkang.(2022).The discovery of a novel series of potential ERR alpha inverse agonists based on p-nitrobenzenesulfonamide template for triple-negative breast cancer in vivo.JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY,37(1),125-134.
MLA	Gao, Zhipei,et al."The discovery of a novel series of potential ERR alpha inverse agonists based on p-nitrobenzenesulfonamide template for triple-negative breast cancer in vivo".JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 37.1(2022):125-134.