Spleen tyrosine kinase (Syk) plays an essential role in the signal transduction of immunoreceptor tyrosine-based activation motifs (ITAM) and the activation of immune cells. R788 disodium is a prodrug of R406, which selectively inhibits Syk with IC50 value of 41 nM. The inhibitory effect of R406 was observed in several Syk-dependent pathways. R406 at 0.001 - 10 μM inhibited anti-IgG-induced degranulation of cultured human mast cells at a dose-dependent manner. It also inhibited the production of TNF-induced by FcγR-crossing-linking in human macrophages. In primary B cells isolated from human peripheral blood, R406 effectively inhibited the upregulation of cell surface CD69 stimulated by B-cell receptor-cross-linking with anti-IgM[4]. In a Eμ-T-cell leukemia 1 (TCL1) mouse model of chronic lymphocytic leukemia (CLL), injection of R788 (80 mg/kg/day) from days 4 to 25 significantly prevented the outgrowth of the leukemia compared to non-treated group. R788 treatment also significantly elevated the survival rate in these treated animals. In B6/C3H mice with overt TCL1-002 leukemia, 15-day treatment of R788 suppressed the increase of circulating leukemic cells seen in control group. Moreover, R788-trreated mice demonstrated significantly reduced amount of phosphorylated SykYY525/526, BLNK, and ERK in leukemic cells, indicating the inhibition of B-cell receptor signaling pathway in vivo[5].
作用机制
R788 disodium is a prodrug of R406, which inhibits the activity of Sky kinase as an ATP-competitive inhibitor with a Ki value of 30 nM[4].
Fostamatinib Disodium 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
human Ramos cells
Cytotoxic assay
Cytotoxicity against human Ramos cells, IC50=0.267 μM
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