Discovery of loperamide as an antagonist of angiopoietin1 and angiopoietin2 by virtual screening

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• 作者：Xing Wen Gong^a ; ^{gongxingwen@163.com} ; Jun Hua Mai^b ; Yu Hong Xu^b ; ^{yhxu@sjtu.edu.cn}
• 关键词：Loperamide ; Antidiarrhea ; Tie2 ; Angiopoietin ; Virtual screening
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：1 April, 2012
• 卷：22
• 期：7
• 页码：2388-2392
• 文件大小：955 K

摘要

The angiopoietin-Tie2 binding and related signal transduction pathways are crucial for vascular angiogenesis, blood vessel integrity and maturation. In this study, we preformed a virtual screening of small molecules targeting to Tie2. The binding site was selected at the extracellular ligand binding region of Tie2, rather than its conventional endocellular ATP binding region. It was found that loperamide, a widely-used antidiarrhea drug, was among the top hits. The binding between loperamide and Tie2 was confirmed by surface plasmon resonance (SPR) assay. Loperamide competitively inhibited the binding of both angiopoietin1 and angiopoietin2. These results indicate that loperamide is an antagonist of angiopoietin1 and angiopoietin2.