Discovery of novel striatal-enriched protein tyrosine phosphatase inhibitors through structure-based virtual screening

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Title
Discovery of novel striatal-enriched protein tyrosine phosphatase inhibitors through structure-based virtual screening
Author(s)
Bonsu Ku; Jin A You; Hye Seon Lee; Ho Chul Shin; H Park; Seung Jun Kim
Bibliographic Citation
Bulletin of Korean Chemical Society, vol. 37, no. 11, pp. 1783-1788
Publication Year
2016
Abstract
Striatal-enriched protein tyrosine phosphatase (STEP) is considered a potential target for the development of therapeutics for neurodegenerative diseases and cocaine addiction. We herein report 10 novel STEP inhibitors identified using a combination of in silico structure-based virtual screening with an accurate solvation free energy term-applied improved scoring function and in vitro phosphatase inhibition assay. These compounds, computationally selected for their advantageous physicochemical properties as drug candidates, exhibited micromolar IC50 values of 3.21-10.6 μM. Enzyme kinetic assays together with structure-based docking simulations suggested that three most potent inhibitors are novel surrogates for phosphotyrosine that are accommodated at the active site of STEP. We expect that identification of these compounds will provide a foundation for further improvement and optimization to develop STEPtargeting drug candidate molecules.
Keyword
InhibitorStriatal-enriched protein tyrosine phosphataseVirtual screening
ISSN
0253-2964
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/bkcs.10974
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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