TAS05567 is a potent, highly selective, and ATP-competitive Syk inhibitor (IC50: 0.37 nM). TAS05567 only shows >70% inhibition of Syk and 4 other kinases (FLT3, JAK2, KDR, and RET with IC50s of 10 nM, 4.8 nM, 600 nM, and 29 nM, respectively) in a panel of 192 kinases.

JAK2:4.8 nM, FLT3:10 nM, KDR:600 nM, RET:29 nM, Syk:0.37 nM

TAS05567 inhibits PLCγ2 (IC50: 23 nM) and Erk1/2 (IC50: 9.8 nM), after stimulation of Ramos cells with anti-IgM. TAS05567 inhibits the formation of mature osteoclasts in a concentration-dependent manner, and osteoclast differentiation is completely suppressed at 30 nM. TAS05567 suppresses both calcium flux (IC50: 27 nM) and histamine release (IC50: 13 nM) induced by cross-linking of FcεRI with IgE and antigen. TAS05567 shows concentration-dependent inhibition of TNF-α production by THP-1 cells stimulated with IgG. When Ramos cells are pretreated with TAS05567 prior to BCR cross-linking by exposure to anti-IgM, there is marked inhibition of the phosphorylation of BLNK. The IC50 of TAS05567 for suppressing the induction of BLNK phosphorylation by anti-IgM is 1.8 nM [1].

TAS05567 (10-30 mg/kg; p.o.; daily; for 9 days; female BALB/c mice) treatment inhibits hind-paw swelling in a dose-dependent manner. The serum MMP-3 levels are obviously lower in both the 10 mg/kg and 30 mg/kg TAS05567 groups than in the vehicle group [1].