Therapeutic prospect of Syk inhibitors.
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.


CONCLUSIONS
Syk kinase inhibition is suggested as a powerful tool for the therapy of different pathologies.
Ruzza
Paolo
P
Institute of Biomolecular Chemistry of CNR, Padova Unit, c/o Dept. Chemical Sciences, University of Padova, via Marzolo 1, Padua, Italy. paolo.ruzza@unipd.it
Biondi
Barbara
B
Calderan
Andrea
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D001665:Binding Sites; D015971:Gene Expression Regulation, Enzymologic; D015316:Genetic Therapy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007938:Leukemia / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D015394:Molecular Structure; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D000072377:Syk Kinase; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase