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New Insights from a Focused Library Approach Aiming at Development of Inhibitors of Dual-Specificity Protein Phosphatases

  • Go Hirai
  • Ayako Tsuchiya
  • Mikiko Sodeoka
Conference paper

Abstract

Protein phosphorylations are important biological reactions participating in intracellular signal transductions [1], and they control a diverse set of cellular events including cell proliferation, cell-cycle regulation, and differentiation. Key players in protein phosphorylations are protein kinases and protein phosphatases, which dynamically control the levels of the phosphorylated proteins in cells. Phosphorylation mainly occurs at the hydroxyl groups of serine, threonine, and tyrosine residues in eukaryotic cells [2]. Protein kinases and phosphatases are classified according to their substrate specificity of phosphorylation and dephosphorylation. Human genome analysis indicates that there are 518 protein kinases [3], which can be divided into 90 tyrosine kinases and 428 serine/threonine kinases [4]. Dysfunction of protein kinases is well established to be implicated in the disruption of normal signal transduction pathways and in tumor formation. Therefore, kinase inhibitors are expected to be useful as biological tools and therapeutic agents, so there is both academic and commercial interest in developing specific inhibitors for certain protein kinases [5]. A number of such inhibitors, such as Gleevec, Iressa, Tarceva, and Sutent, have been approved as therapeutic agents by the Food and Drug Administration in the United States.

Keywords

Protein Phosphatase Core Structure Potent Inhibitory Activity Hydrophobic Alkyl Chain Enzyme Selectivity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported in part by a grant from the Uehara Memorial Foundation (Japan) and project funding from RIKEN (Japan). We would like to thank Prof. Hiroyuki Osada, Prof. Siro Simizu, Prof. Takeo Usui, Dr. Keisuke Ishida, and Dr. Ngit Shin Lai (RIKEN, Japan) for their collaboration in this work. We are also grateful to our co-workers at RIKEN, Ms. Kana Oonuma, Mr. Yusuke Koyama, Dr. Yuko Otani, and other coworkers and collaborators listed in the references, for their contributions.

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Copyright information

© Springer 2012

Authors and Affiliations

  1. 1.Synthetic Organic Chemistry Laboratory, RIKEN Advanced Science InstituteWako, SaitamaJapan

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