Structure-based virtual screening approach to the discovery of novel inhibitors of eyes absent 2 phosphatase with various metal chelating moieties.

Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Korea.
Chemical Biology &amp Drug Design (Impact Factor: 2.51). 07/2011; 78(4):642-50. DOI: 10.1111/j.1747-0285.2011.01192.x
Source: PubMed

ABSTRACT Despite a series of persuasive experimental evidence for the involvement of eyes absent protein tyrosine phosphatases in various human cancers, no small-molecule inhibitor has been reported so far. We have identified seven novel inhibitors of eyes absent homologue 2 (Eya2) with IC(50) values ranging from 1 to 70 μm by the virtual screening with docking simulations and enzyme inhibition assay. Atomic charges of the active-site Mg(2+) ion complex are calculated to enhance the accuracy of docking simulations. The newly discovered inhibitors are structurally diverse and have various chelating groups for the Mg(2+) ion. The interactions with the amino acid residues responsible for the stabilizations of the inhibitors in the active site of Eya2 are addressed in detail.

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