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

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Chembiomolecular Science

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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.

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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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Authors and Affiliations

  1. Synthetic Organic Chemistry Laboratory, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Go Hirai, Ayako Tsuchiya & Mikiko Sodeoka

Authors
  1. Go Hirai
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  2. Ayako Tsuchiya
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  3. Mikiko Sodeoka
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Corresponding author

Correspondence to Mikiko Sodeoka .

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Editors and Affiliations

  1. Institute of Microbial Chemistry, Kamioosaki 3-14-23, Tokyo, 141-0021, Japan

    Masakatsu Shibasaki

  2. The University of Tokyo, Department of Pharmacology, Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, 113-0033, Japan

    Masamitsu Iino

  3. RIKEN Advanced Science Institute, Antibiotics Laboratory, Chemical Biology Core Facility, 2-1, Hirosawa, Wako, 351-0198, Saitama, Japan

    Hiroyuki Osada

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© 2012 Springer

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Hirai, G., Tsuchiya, A., Sodeoka, M. (2012). New Insights from a Focused Library Approach Aiming at Development of Inhibitors of Dual-Specificity Protein Phosphatases. In: Shibasaki, M., Iino, M., Osada, H. (eds) Chembiomolecular Science. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54038-0_7

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