Spleen tyrosine kinase (Syk) is a cytosolic non-receptor protein tyrosine kinase (PTK) and is mainly expressed in hematopoietic cells. Syk was recognized as a critical element in the B-cell receptor signaling pathway. Syk is also a key component in signal transduction from other immune receptors like Fc receptors and adhesion receptors[3]. R112 is an ATP-competitive inhibitor of Syk kinase with a Ki of 96 nM. R112 inhibits Syk kinase activity with an IC50 of 226 nM[4]. R112 does not inhibit phosphorylation of the Lyn target Syk (Y352), but inhibits the phosphorylation of the Syk target LAT (Y191), indicating that Syk kinase is the primary target. R112 is able to completely inhibit all three IgE-induced mast cell functions: degranulation, lipid mediator production, and cytokine production. R112 potently, completely, and rapidly abrogated all mast cell activation cascades triggered by IgE receptor cross-linking. R112 also blocks leukotriene C4 production and all proinflammatory cytokines tested. Its onset of action is immediate, and the inhibition is reversible[4].
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