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

Cited 14 time in scopus
Metadata Downloads
Title
Structure-based virtual screening approach to the discovery of novel inhibitors of eyes absent 2 phosphatase with various metal chelating moieties
Author(s)
H Park; S K Jung; Keum Ran Yu; J H Kim; Yong Sam KimJeong Heon KoByoung Chul ParkSeung Jun Kim
Bibliographic Citation
Chemical Biology & Drug Design, vol. 78, no. 4, pp. 642-650
Publication Year
2011
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 70μm 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. We have discovered novel inhibitors of Eyes Absent 2 phosphatases by means of the structure-based virtual screening and in vitro enzyme assay. Each inhibitor has its own chelating group for the active-site Mg 2+ ion.
Keyword
Chelating groupDockingEyes absent protein tyrosine phosphataseInhibitorVirtual screening
ISSN
1397-002X
Publisher
Wiley
DOI
http://dx.doi.org/10.1111/j.1747-0285.2011.01192.x
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.