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Fostamatinib Disodium

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Chemical Structure| 1025687-58-4 同义名 : R935788;NSC 745942;Fostamatinib;R788 (sodium salt);Tamatinib Fosdium;R788(Disodium)
CAS号 : 1025687-58-4
货号 : A144826
分子式 : C23H24FN6Na2O9P
纯度 : 99%+
分子量 : 624.423
MDL号 : MFCD15146370
存储条件：

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(32.03 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 1 mg/mL(1.6 mM)
动物实验配方：

PO 0.5% CMC-Na 56 mg/mL suspension

生物活性
靶点

  • Syk

    Syk, IC50:41 nM
描述 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].
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 23151054
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.60mL

0.32mL

0.16mL

8.01mL

1.60mL

0.80mL

16.01mL

3.20mL

1.60mL
参考文献

[1]McAdoo SP, Tam FW, et al. Fostamatinib Disodium. Drugs Future. 2011;36(4):273.

[2]Bahjat FR, Pine PR, et al. An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupus. Arthritis Rheum. 2008 May;58(5):1433-44.

[3]Pine PR, Chang B, et al. Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor. Clin Immunol. 2007 Sep;124(3):244-57. Epub 2007 May 29.

[4]Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008.

[5]Suljagic M, Longo PG, Bennardo S, Perlas E, Leone G, Laurenti L, Efremov DG. The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Eμ- TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling. Blood. 2010 Dec 2;116(23):4894-905.