Therapeutic prospect of Syk inhibitors

Expert Opin Ther Pat. 2009 Oct;19(10):1361-76. doi: 10.1517/13543770903207039.

Abstract

Background: The non-receptor spleen tyrosine kinase (Syk; EC 2.7.10.2) is involved in signal transduction in a variety of cell types. In particular, it is a key mediator of immune receptors signaling in host inflammatory cells (B cells, mast cells, macrophages and neutrophils), important for both allergic and antibody-mediated autoimmune diseases. Deregulated Syk kinase activity also allows growth factor-independent proliferation and transforms bone marrow-derived pre-B cells that are able to induce leukemia. Consequently, the development of Syk kinase inhibitors could conceivably treat these disorders and so they have became a major focus in the pharmaceutical and biotech industry.

Objective: In this review, we analyze the structure and role of Syk kinase, the use of small molecules, interacting with ATP-binding site, as inhibitors of kinase activity and finally the potential of using inhibitors of Syk kinase expression to attenuate pathological conditions.

Conclusion: Syk kinase inhibition is suggested as a powerful tool for the therapy of different pathologies.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Autoimmune Diseases / enzymology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / therapy*
  • Binding Sites
  • Gene Expression Regulation, Enzymologic
  • Genetic Therapy*
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leukemia / enzymology
  • Leukemia / genetics
  • Leukemia / therapy*
  • Molecular Structure
  • Protein Conformation
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction / drug effects
  • Structure-Activity Relationship
  • Syk Kinase
  • Treatment Outcome

Substances

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