Discovery of Novel Striatal-enriched Protein Tyrosine Phosphatase Inhibitors Through Structure-based Virtual Screening
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 wit...
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Published in | Bulletin of the Korean Chemical Society Vol. 37; no. 11; pp. 1783 - 1788 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Weinheim
Wiley-VCH Verlag GmbH & Co. KGaA
01.11.2016
Wiley‐VCH Verlag GmbH & Co. KGaA 대한화학회 |
Subjects | |
Online Access | Get full text |
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Summary: | 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 STEP‐targeting drug candidate molecules. |
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Bibliography: | World Class Institute program - No. WCI 2009-002 ArticleID:BKCS10974 KRIBB Research Initiative Program ark:/67375/WNG-Q571SGZ0-6 Ministry of Science, ICT and Future Planning National Research Foundation of Korea - No. 2014M3A9B6070243; No. 2015M3A9B5030308 istex:23E551D0C44163120D54151355A7F39BDA150A44 G704-000067.2016.37.11.027 http://onlinelibrary.wiley.com/doi/10.1002/bkcs.10974/abstract |
ISSN: | 1229-5949 0253-2964 1229-5949 |
DOI: | 10.1002/bkcs.10974 |