Inhibitors of switch kinase 'spleen tyrosine kinase' in inflammation and immune-mediated disorders: a review

Eur J Med Chem. 2013 Sep:67:434-46. doi: 10.1016/j.ejmech.2013.04.070. Epub 2013 Jul 12.

Abstract

Spleen tyrosine kinase (Syk), a member of Syk family of non-receptor protein tyrosine kinases plays a significant role in the immune cell signaling in B cells, mast cells, macrophages and neutrophils. Anomalous regulation of this kinase can lead to different allergic disorders and antibody-mediated autoimmune diseases such as rheumatoid arthritis, asthma, psoriasis and allergic rhinitis. Being involved in the growth and survive mechanism of B cells, its inhibition can be beneficial in B-cell lymphoma. Thus, Syk can be sited as a therapeutically relevant target for various allergic and autoimmune disorders. This review article describes the structure of Syk and its role in B-cell signaling. In addition to this, data regarding small molecule inhibitors of Syk has also been reviewed from different papers and patents published.

Keywords: Asthma; Autoimmune diseases; B-Cell lymphoma; Inflammation; Psoriasis; Spleen tyrosine kinase.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Dose-Response Relationship, Drug
  • Humans
  • Inflammation / drug therapy*
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Models, Biological
  • Molecular Structure
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Structure-Activity Relationship
  • Syk Kinase

Substances

  • Intracellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase