Syk inhibitors

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  • CHIHARA Kazuyasu
    Division of Genome Science and Microbiology, Faculty of Medical Sciences, University of Fukui Organization for Life Science Advancement Programs, University of Fukui
  • KIMURA Yukihiro
    Division of Genome Science and Microbiology, Faculty of Medical Sciences, University of Fukui Division of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui
  • HONJO Chisato
    Division of Genome Science and Microbiology, Faculty of Medical Sciences, University of Fukui Division of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui
  • TAKEUCHI Kenji
    Division of Genome Science and Microbiology, Faculty of Medical Sciences, University of Fukui Organization for Life Science Advancement Programs, University of Fukui
  • SADA Kiyonao
    Division of Genome Science and Microbiology, Faculty of Medical Sciences, University of Fukui Organization for Life Science Advancement Programs, University of Fukui

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  • チロシンキナーゼSykの生理機能とその阻害薬

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  Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in University of Fukui in 1991. Syk is most highly expressed by haemopoietic cells and known to play crucial roles in the signal transduction through various immunoreceptors of the adaptive immune response. However, recent reports demonstrate that Syk also mediates other biological functions, such as innate immune response, osteoclast maturation, platelet activation and cellular adhesion. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Because of its critical roles on the cellular functions, the development of Syk inhibitors for clinical use has been desired. Although many candidate compounds were produced, none of them had progressed to clinical trials. However, novel Syk inhibitors were finally developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure and function of Syk, and then the novel Syk inhibitors and their current status. In addition, we will introduce our research focused on the functions of Syk on Dectin-1-mediated mast cell activation.<br>

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