Fostamatinib Disodium

CAS No. : 1025687-58-4

Fostamatinib Disodium,1025687-58-4
Product Details
For research use only. Not Intended for Therapeutic Use!
Cat No:I000167
Synonyms:disodium;[6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-3-oxopyrido[3,2-b][1,4]oxazin-4-yl]methyl phosphate
Molecular Formula:C₂₃H₂₄FN₆O₉PNa₂
Molecular Weight:624.42
Target:Spleen Tyrosine Kinase (Syk)
IC50:41 nM
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Appearance:A crystalline solid
Cat No:I000167
Cas No:1025687-58-4
Product-Name:Fostamatinib Disodium
MDL No:MFCD16628163

R788 (Fostamatinib) disodium, a prodrug of the active metabolite R406, is a potent Syk inhibitor with IC50 of 41 nM.

in vitro: R788 is a methylene phosphate prodrug of R406, which can be rapidly converted to R406 in vivo. R406 (in vitro active form of R788) selectively inhibits Syk-dependent signaling with EC50 values ranging from 33 nM to 171 nM, more potently than Syk-independent pathways in different cells [1]. R406 inhibits cellular proliferation of a variety of diffuse large B-cell lymphoma (DLBCL) cell lines with EC50 values ranging from 0.8 μM to 8.1 μM [2]. R406 treatment reduces basal phosphorylation of BLNK, Akt, glycogen synthase kinase-3 (GSK-3), forkhead box O (FOXO) and ERK not only in cells with high (TCL-002) but also in cells with low levels of phosphorylated Syk (TCL1-551). In addition, R406 completely inhibits the anti-IgM induced Bcr signal in TCL1 leukemias. Despite the higher levels of constitutively active Syk in TCL1 leukemias, R406 is not selectively cytotoxic to the leukemic cells [3]. 

in vivo: R788 effectively inhibits BCR signaling in vivo, resulting in reduced proliferation and survival of the malignant B cells and significantly prolonged survival of the treated animals [3]. 

[1]. Braselmann, S., et al., R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther, 2006. 319(3): p. 998-1008. 

[2]. Chen, L., et al., SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood, 2008. 111(4): p. 2230-7. 

[3]. Suljagic, M., et al., The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Emu- TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling. Blood, 2010. 116(23): p. 4894-905.

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