Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase that upon phosphorylation binds to immunoreceptor tyrosine-based activation motifs of FcRγ chains and mediates downstream signaling related to platelet function and inflammation. R788 is a prodrug of R406 , an inhibitor of Syk (Ki = 30 nM). R788 conversion to the biologically active R406 is catalyzed by the action of alkaline phosphatases present on the apical brush-border of the membranes of intestinal enterocytes. It produces anti-inflammatory and immunomodulating effects by inhibiting Syk-mediated IgG Fcγ receptor signaling, which prevents activation of mast cells, macrophages, and B cells, as well as related inflammatory responses. R788 has undergone clinical evaluation for efficacy in the treatment of rheumatoid arthritis.
