R112 Syk inhibitor

R112 inhibits degranulation induced by anti-IgE cross-linking in mast cells (tryptase release, effective concentration for 50% inhibition [EC50] = 353 nmol/L) or basophils (histamine release, EC50 = 280 nmol/L), and by allergen (dust mite) in basophils (histamine release, EC50 = 490 nmol/L). This compound also blocks leukotriene C4 production and all proinflammatory cytokines tested. Its onset of action is immediate, and the inhibition is reversible. It is able to completely inhibit all three IgE-induced mast cell functions: degranulation, lipid mediator production, and cytokine production. This chemical 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 of this compound. Most phosphorylation events downstream of Syk are inhibited with similar potency by this chemical. In vitro kinase assays do not always correlate with the corresponding activity inside cells. It inhibits the Lyn kinase in vitro assay with an IC50 of 0.3 μmol/L; however, as mentioned previously, in CHMCs (Cultured human mast cells), this compound does not inhibit the phosphorylation of Syk (Y352), and therefore most likely does not inhibit Lyn activity[1].