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