Discovery of Cyclic Peptidomimetic Ligands Targeting the Extracellular Domain of EGFR

doi:10.1021/acs.jmedchem.1c00607

	Discovery of Cyclic Peptidomimetic Ligands Targeting the Extracellular Domain of EGFR
	Zheng, Mengmeng 1; Li, Chunpu 1,2,3; Zhou, Mi 1; Jia, Ru 2,3; Cai, Gang 2,3; She, Fengyu 1; Wei, Lulu 1; Wang, Shaohui 4; Yu, Jie 5; Wang, Dingyan 5
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2021-08-12
卷号	64 期号:15 页码:11219-11228
ISSN号	0022-2623
DOI	10.1021/acs.jmedchem.1c00607
通讯作者	Li, Qi(qili@shutcm.edu.cn) ; Wang, Yan(yanwang@shutcm.edu.cn) ; Cai, Jianfeng(Jianfengcai@usf.edu)
英文摘要	It is very promising to target the extracellular domain of epidermal growth factor receptor (EGFR) for developing novel and selective anticancer therapies. Herein, we report the discovery of a novel small molecule, M-2-5, from a one-bead-two-compound (OBTC) cyclic gamma-AApeptide library. The molecule was found to bind tightly to the extracellular domain of EGFR. Intriguingly, this molecule could also effectively antagonize EGF-stimulated EGFR phosphorylation and downstream signal transduction. Furthermore, together with its remarkable resistance to proteolytic degradation, M-2-5 was shown to effectively inhibit cell proliferation and migration in vitro and suppresses the growth of tumor in the A549 xenograft model in vivo, highlighting its potential therapeutic application for cancer treatment.
资助项目	USF ; National Natural Science Foundation of China[81520108031] ; National Natural Science Foundation of China[81573764] ; National Natural Science Foundation of China[81774095] ; Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines in Shanghai[2017BR031] ; Threeyear Plan for the Development of TCM[ZY (2018-2020). CCCX-2003-03]
WOS关键词	EPIDERMAL-GROWTH-FACTOR ; FACTOR RECEPTOR ; SIGNAL-TRANSDUCTION ; GAMMA-AAPEPTIDES ; PEPTIDE LIGAND ; CANCER ; BINDING ; MUTATIONS ; GEFITINIB ; THERAPY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000685644300039
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297648]
专题	中国科学院上海药物研究所
通讯作者	Li, Qi; Wang, Yan; Cai, Jianfeng
作者单位	1.Univ S Florida, Dept Chem, Tampa, FL 33620 USA 2.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Med Oncol, Shanghai 201203, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Canc Inst Med, Shanghai 201203, Peoples R China 4.Univ S Florida, Morsani Coll Med, Dept Mol Med, Tampa, FL 33612 USA 5.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 6.Univ S Florida, Coll Pharm, Dept Pharmaceut Sci, Tampa, FL 33612 USA 7.Shanghai Univ Tradit Chinese Med, Acad Integrat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zheng, Mengmeng,Li, Chunpu,Zhou, Mi,et al. Discovery of Cyclic Peptidomimetic Ligands Targeting the Extracellular Domain of EGFR[J]. JOURNAL OF MEDICINAL CHEMISTRY,2021,64(15):11219-11228.
APA	Zheng, Mengmeng.,Li, Chunpu.,Zhou, Mi.,Jia, Ru.,Cai, Gang.,...&Cai, Jianfeng.(2021).Discovery of Cyclic Peptidomimetic Ligands Targeting the Extracellular Domain of EGFR.JOURNAL OF MEDICINAL CHEMISTRY,64(15),11219-11228.
MLA	Zheng, Mengmeng,et al."Discovery of Cyclic Peptidomimetic Ligands Targeting the Extracellular Domain of EGFR".JOURNAL OF MEDICINAL CHEMISTRY 64.15(2021):11219-11228.