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Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase that upon phosphorylation binds to immunoreceptor tyrosine-based activation motifs and mediates downstream signaling. Syk inhibitor II is a cell-permeable, pyrimidine-carboxamide compound that selectively and reversibly blocks Syk (IC50 = 41 nM) in an ATP-competitive manner. It is much less potent against PKCε, PKCβII, ZAP-70, Btk, and Itk (IC50s = 5.1, 11, 11.2, 15.5, and 22.6 µM, respectively). Syk inhibitor II has been shown to prevent FcεRI-mediated 5-HT release in RBL-2H3 cells in vitro (IC50 = 460 nM) and to inhibit passive cutaneous anaphylaxis reactions in mice (ID50 = 13.2 mg/kg, s.c.).

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