Syk kinase inhibitors in allergic diseases.
Recent advances in the understanding of allergic mechanisms have highlighted the role of immunoglobulin E (IgE) signaling in the mast cell. One of the most important kinases in the IgE signaling pathway is spleen tyrosine kinase (Syk) which has a critical function early in the signaling cascade following binding of allergen to receptor bound IgE on the mast cell. A number of Syk inhibitors have now been developed which have been shown to effectively inhibit IgE-driven mast cell degranulation and release of inflammatory cytokines in vitro and inhibit allergic responses in a variety of in vivo models. In humans, allergen-driven symptoms were reduced in allergic rhinitic patients exposed to tree pollen in an outdoor environment following intranasal dosing of the Syk inhibitor R-112. Syk therefore represents a promising target for therapeutic intervention in allergic diseases.
Denyer
Jane
J
Respiratory CEDD, GlaxoSmithKline Medicines Research Centre, Stevenage, Herts SG1 2NY, UK. jane.c.denyer@gsk.com
Patel
Vipul
V
D000818:Animals; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D008407:Mast Cells / Q000502:physiology; D008954:Models, Biological; D015394:Molecular Structure; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology*; D000072377:Syk Kinase
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase