Drug discovery and protein tyrosine phosphatases

Blaskovich, M. A. T. (2009) Drug discovery and protein tyrosine phosphatases. Current Medicinal Chemistry, 16 17: 2095-2176. doi:10.2174/092986709788612693

Author Blaskovich, M. A. T.
Title Drug discovery and protein tyrosine phosphatases
Journal name Current Medicinal Chemistry   Check publisher's open access policy
ISSN 0929-8673
Publication date 2009-06-01
Year available 2009
Sub-type Article (original research)
DOI 10.2174/092986709788612693
Open Access Status Not Open Access
Volume 16
Issue 17
Start page 2095
End page 2176
Total pages 82
Editor Atta-ur Rahman
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Language eng
Subject C1
970103 Expanding Knowledge in the Chemical Sciences
030406 Proteins and Peptides
Abstract Protein tyrosine phosphatases (PTPs) play a critical role in physiological signaling pathways by controlling the level of tyrosine phosphorylation. The past decade has seen a vast increase in both academic and industrial interest in PTPs and their relevance as potential therapeutic targets, with several PTP inhibitors recently entering clinical trials. Despite these developments, there are numerous examples of failed PTP drug discovery programs, such that PTPs have attained a reputation as `undruggable' targets. This review attempts to illustrate the many obstacles that must be overcome to successfully develop a PTP drug, ranging from validation of PTPs as therapeutic targets to the difficulties of assessing the true inhibitory nature of apparently well-behaved compounds, along with the need to balance the physiocochemical properties required for active site binding with the characteristics needed for in vivo activity. A number of examples of structure-based design are presented, along with cautionary tales of PTP inhibitor programs that have failed due to unexpected shortcomings.
Keyword Drug Discovery
Protein tyrosine phosphatase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 76 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 76 times in Scopus Article | Citations
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Created: Tue, 30 Mar 2010, 22:35:45 EST by Susan Allen on behalf of Institute for Molecular Bioscience