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R935788 (Fostamatinib disodium)

Cat No.
CEI-0266
Description
R935788 (Fostamatinib disodium) can potently inhibit syk with IC50 of 41 nM.
CAS No.
1025687-58-4
Molecular Weight
624.42
Purity
>99%
Storage
2 years at -20centigrade Powder
Targets
syk
Molecular Formula
C23H24FN6O9P.2Na
Chemical Name
2H-Pyrido[3,2-b]-1,4-oxazin-3(4H)-one, 6-[[5-fluoro-2-[(3,4,5-trimethoxyphenyl)amino]-4-pyrimidinyl]amino]-2,2-dimethyl-4-[(phosphonooxy)methyl]-, sodium salt (1:2)
Solubility
DMSO 0.4 mg/mL Water
In vitro
As a prodrug of the spleen tyrosine kinase (Syk) inhibitor R406, fostamatinib can potently inhibit SYK with IC50 of 41 nM. As Syk is a key mediator of Fc and B-cell receptor signaling in inflammatory cells (B-cells, mast cells, macrophages and neutrophils), fostamatinib can significantly reduce major inflammatory mediators such as TNF-alpha, IL-1, IL-6 and IL-18, leading to reduced inflammation and bone degradation in models of RA.
In vivo
Fostamatinib can also inhibit antigen-dependent B-cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL). 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. The growth-inhibitory effect of R788 occurs despite the relatively modest cytotoxic effect in vitro and is independent of basal Syk activity, suggesting that R788 functions primarily by inhibiting antigen-dependent BCR signals. In a phase II clinical trial, fostamatinib treatment effectively improved American College of Rheumatology response rates in patients with RA.
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