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

Xing Wen Gong, Jun Hua Mai, Yu Hong Xu

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2388-2392
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number7
DOIs
StatePublished - Apr 1 2012

Keywords

  • Angiopoietin
  • Antidiarrhea
  • Loperamide
  • Tie2
  • Virtual screening

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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