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.