title: Syk inhibitors.
abstract: 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.
authors.affiliation: Division of Genome Science and Microbiology, Faculty of Medical Sciences, University of Fukui.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Chihara
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kimura
authors.forename: Chisato
authors.initials: C
authors.lastname: Honjo
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Kiyonao
authors.initials: K
authors.lastname: Sada
mesh_terms: D000631:Aminopyridines; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D008407:Mast Cells / Q000201:enzymology; D009025:Morpholines; D010078:Oxazines / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines; D000072377:Syk Kinase
chemical_list: D000631:Aminopyridines; D047908:Intracellular Signaling Peptides and Proteins; D009025:Morpholines; D010078:Oxazines; D011725:Pyridines; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C523665:fostamatinib