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

Article Details

Citation

Gong XW, Mai JH, Xu YH

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

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2388-92. doi: 10.1016/j.bmcl.2012.02.036. Epub 2012 Feb 22.

PubMed ID
22406116 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AmpicillinAngiopoietin-1 receptorProteinHumans
Unknown
Not AvailableDetails
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AmpicillinAngiopoietin-1 receptorKd (nM)82000N/AN/ADetails