| Description |
TAS05567 (TAS-5567) is a novel potent, selective, orally available Spleen tyrosine kinase (Syk) inhibitor with IC50 of 0.37 nM; shows >70% inhibition of Syk and 4 other kinases in a panel of 192 kinases, more selective and potent than R406; suppresses induction of BLNK phosphorylation by anti-IgM in Ramos cells (IC50=1.8 nM); inhibits BCR-dependent signal transduction in Ramos cells, FcγR-mediated TNF-α production in THP-1 cells, and FcεR-mediated histamine release from RBL-2H3 cells; suppresses hind-paw swelling in a dose-dependent manner, markedly reduces histopathologic scores in rheumatoid arthritis models.
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| Related Catalog |
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| Target |
IC50: 0.37 nM (Syk); 10 nM (FLT3), 4.8 nM (JAK2), 600 nM (KDR) and 29 nM (RET)[1]
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| 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].
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| 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]. Animal Model: Female BALB/c mice (7-8 weeks old) injected with collagen antibody[1] Dosage: 10 mg/kg, 30 mg/kg Administration: Oral administration; daily; for 9 days Result: Suppressed hind-paw swelling in a dose-dependent manner.
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| References |
[1]. Hayashi H, et al. TAS05567, a Novel Potent and Selective Spleen Tyrosine Kinase Inhibitor, Abrogates Immunoglobulin-Mediated Autoimmune and Allergic Reactions in Rodent Models. J Pharmacol Exp Ther. 2018 Jul;366(1):84-95.
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