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A Guanidine-Based Synthetic Compound Suppresses Angiogenesis via Inhibition of Acid Ceramidase

文献类型：期刊论文

作者Cho, Sung Min1; Lee, Hyung Keun1; Liu, Qing2,3; Wang, Ming-Wei2,3,4; Kwon, Ho Jeong1
刊名ACS CHEMICAL BIOLOGY
出版日期2019
卷号14期号:1页码:11-19
ISSN号1554-8929
DOI10.1021/acschembio.8b00558
通讯作者Wang, Ming-Wei(mwwang@simm.ac.cn) ; Kwon, Ho Jeong(kwonhj@yonsei.ac.kr)
英文摘要Angiogenesis generates new blood vessels from pre-existing vessels. Tumors induce the formation of new blood vessels to ensure sufficient oxygen and nutrients for their growth. Normally, angiogenesis is induced by various pro-angiogenesis factors, including vascular endothelial growth factor (VEGF). Inhibition of VEGF is a promising approach to cancer treatment. A guanidine-based synthetic compound, E2, was identified as a potent hit from 68 guanidine-based derivatives by screening for angiogenesis inhibitors showing antiproliferative activity in human umbilical vein endothelial cells (HUVECs). To explore the mode of action of E2, target proteins were investigated using phage display biopanning, and acid ceramidase 1 (ASAH1) was identified as an E2-binding protein. Drug affinity responsive target stability (DARTS) and ASAH1 activity assays revealed the direct binding of E2 to ASAH1. Moreover, siRNA knockdown of ASAH1 demonstrated its role as an angiogenesis factor. Consequently, E2 inhibited chemoinvasion and tube formation of HUVECs in a dose-dependent manner. E2 also potently suppressed neo-vascularization of chorioallantoic membranes in vivo. Collectively, these data suggest that E2 is a novel angiogenesis inhibitor and ASAH1 is proposed to be a new antiangiogenesis target.
WOS关键词ACTIVATION ; DERIVATIVES ; GROWTH ; TARGET ; CANCER ; AGENTS
资助项目National Research Foundation of Korea (MSIP)[2015K1A1A2028365] ; National Research Foundation of Korea (MSIP)[2015M3A9C4076321] ; National Research Foundation of Korea (MSIP)[2016K2A9A1A03904900] ; Brain Korea 21 Plus Project ; Chinese Ministry of Health[2012ZX09304-011] ; Chinese Ministry of Health[2013ZX09507-001] ; Chinese Ministry of Health[2013ZX09507-002]
WOS研究方向Biochemistry & Molecular Biology
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000456632500002
源URL[http://119.78.100.183/handle/2S10ELR8/290680]  
专题中国科学院上海药物研究所
通讯作者Wang, Ming-Wei; Kwon, Ho Jeong
作者单位1.Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biotechnol, Chem Genom Global Res Lab, Seoul 120749, South Korea
2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
4.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Cho, Sung Min,Lee, Hyung Keun,Liu, Qing,et al. A Guanidine-Based Synthetic Compound Suppresses Angiogenesis via Inhibition of Acid Ceramidase[J]. ACS CHEMICAL BIOLOGY,2019,14(1):11-19.
APA Cho, Sung Min,Lee, Hyung Keun,Liu, Qing,Wang, Ming-Wei,&Kwon, Ho Jeong.(2019).A Guanidine-Based Synthetic Compound Suppresses Angiogenesis via Inhibition of Acid Ceramidase.ACS CHEMICAL BIOLOGY,14(1),11-19.
MLA Cho, Sung Min,et al."A Guanidine-Based Synthetic Compound Suppresses Angiogenesis via Inhibition of Acid Ceramidase".ACS CHEMICAL BIOLOGY 14.1(2019):11-19.

入库方式： OAI收割

来源：上海药物研究所

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