Discovery of N-substituted sulfamoylbenzamide derivatives as novel inhibitors of STAT3 signaling pathway based on Niclosamide

doi:10.1016/j.ejmech.2021.113362

科研成果详情

题名	Discovery of N-substituted sulfamoylbenzamide derivatives as novel inhibitors of STAT3 signaling pathway based on Niclosamide
作者	Wang, Xuebao1,2; Wu, Kaiqi 2; Fang, Longcheng 2; Yang, Xiaojiao2; Zheng, Nan 2; Du, Zongxuan 2; Lu, Ying2; Xie, Zixin2; Liu, Zhiguo2; Zuo, Zhigui1; Ye, Faqing1,2
发表日期	2021-06-05
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	N-substituted sulfamoylbenzamide STAT3 inhibitors Niclosamide Anti-tumor activity
其他关键词	CELL LUNG-CANCER ; TRANSDUCER ; CARCINOMA ; ACTIVATOR ; KNOCKOUT ; GROWTH ; POTENT
摘要	Signal transducer and activator of transcription 3 (STAT3) has been confirmed as an attractive therapeutic target for cancer therapy. Herein, we designed and synthesized a series of N-substituted Sulfamoylbenzamide STAT3 inhibitors based on small-molecule STAT3 inhibitor Niclosamide. Compound B12, the best active compound of this series, was identified as an inhibitor of IL-6/STAT3 signaling with an IC50 of 0.61-1.11 mu M in MDA-MB-231, HCT-116 and SW480 tumor cell lines with STAT3 overexpression, by inhibiting the phosphorylation of STAT3 of Tyr705 residue and the expression of STAT3 downstream genes, inducing apoptosis and inhibiting the migration of cancer cells. Furthermore, in vivo study revealed that compound B12 suppressed the MDA-MB-231 xenograft tumor growth in nude mice at the dose of 30 mg/kg (i.g.), which has better antitumor activity than the positive control Niclosamide. More importantly, B12 is an orally bioavailable anticancer agent as a promising candidate for further development. (c) 2021 Elsevier Masson SAS. All rights reserved.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81373262]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LY16B020010, LY17B020008, LY20H300003, LY21B020011]
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
出版地	ISSY-LES-MOULINEAUX
ISSN	0223-5234
EISSN	1768-3254
卷号	218 页码:113362
DOI	10.1016/j.ejmech.2021.113362
页数	15
WOS类目	Chemistry, Medicinal
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000646195900007
收录类别	SCIE ; PUBMED ; SCOPUS ; IC
URL	查看原文
PubMed ID	33774344
SCOPUSEID	2-s2.0-85103334873
自科自定义期刊分类	T3(B)类
通讯作者地址	[Ye, Faqing]Department of Colorectal Surgery,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China ; [Zuo, Zhigui]Department of Colorectal Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Pharmacology;Drug Discovery;Organic Chemistry
TOP期刊	TOP期刊
引用统计	被引频次：7[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/1515
专题	附属第一医院_肛肠外科药学院（分析测试中心）第一临床医学院（信息与工程学院）、附属第一医院
通讯作者	Zuo, Zhigui; Ye, Faqing
作者单位	1.Department of Colorectal Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China; 2.School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 药学院（分析测试中心）
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Wang, Xuebao,Wu, Kaiqi,Fang, Longcheng,et al. Discovery of N-substituted sulfamoylbenzamide derivatives as novel inhibitors of STAT3 signaling pathway based on Niclosamide[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2021,218:113362.
APA	Wang, Xuebao., Wu, Kaiqi., Fang, Longcheng., Yang, Xiaojiao., Zheng, Nan., ... & Ye, Faqing. (2021). Discovery of N-substituted sulfamoylbenzamide derivatives as novel inhibitors of STAT3 signaling pathway based on Niclosamide. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 218, 113362.
MLA	Wang, Xuebao,et al."Discovery of N-substituted sulfamoylbenzamide derivatives as novel inhibitors of STAT3 signaling pathway based on Niclosamide".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 218(2021):113362.