TAS05567

TAS05567 is a potent, highly selective, ATP-competitive and orally active Syk inhibitor with an IC₅₀ of 0.37 nM. In a panel of 192 kinases, 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). TAS05567 can be used for humoral immune-mediated inflammatory conditions such as autoimmune and allergic diseases^[1]. IC50 & Target: IC50: 0.37 nM (Syk); 10 nM (FLT3), 4.8 nM (JAK2), 600 nM (KDR) and 29 nM (RET)^[1] In Vitro: When Ramos cells (human B lymphoma cells) are pretreated with TAS05567 prior to BCR cross-linking by exposure to anti-IgM, there is marked inhibition of the phosphorylation of BLNK, an adaptor protein phosphorylated by activated Syk. The IC₅₀ of TAS05567 for suppressing induction of BLNK phosphorylation by anti-IgM is 1.8 nM. TAS05567 also inhibits PLCγ2 (IC₅₀ of 23 nM) and Erk1/2 (IC₅₀ of 9.8 nM), after stimulation of Ramos cells with anti-IgM^[1].
TAS05567 shows concentration-dependent inhibition of TNF-α production by THP-1 cells stimulated with IgG^[1].
TAS05567 suppresses both calcium flux (IC₅₀ of 27 nM) and histamine release (IC₅₀ of 13 nM) induced by cross-linking of FcεRI with IgE and antigen^[1].
TAS05567 inhibits the formation of mature osteoclasts in a concentration-dependent manner, and osteoclast differentiation is completely suppressed at 30 nM^[1]. In Vivo: TAS05567 (10-30 mg/kg; oral administration; daily; for 9 days; female BALB/c mice) treatment suppresses hind-paw swelling in a dose-dependent manner. The serum MMP-3 levels are significantly lower in both the 10 mg/kg and 30 mg/kg TAS05567 groups than in the vehicle group^[1].