914295-16-2

914295-16-2 structure

Name: R788 (disodium hexahydrate)
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]-, disodium salt, hexahydrate
CAS Number: 914295-16-2
Molecular Formula: C₂₃H₂₄FN₆Na₂O₉P_.6H₂O
Molecular Weight: 732.51
Catalog: Signaling Pathways Protein Tyrosine Kinase/RTK Syk
Create Date: 2018-10-05 19:37:31
Modify Date: 2024-01-02 17:13:39
Fostamatinib disodium hexahydrate (R788 disodium hexahydrate), a prodrug of the active metabolite R406, is a potent Syk inhibitor with IC50 of 41 nM.

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]-, disodium salt, hexahydrate
Synonyms	FostaMatinib DisodiuM Hexahydrate R788 disodium hexahydrate R788 (disodium hexahydrate)

Description	Fostamatinib disodium hexahydrate (R788 disodium hexahydrate), a prodrug of the active metabolite R406, is a potent Syk inhibitor with IC50 of 41 nM.
Related Catalog	Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Syk Research Areas >> Inflammation/Immunology
Target	IC50 Value: 41 nM [1]Target: Syk
In Vitro	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	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].
References	[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.

Molecular Formula	C₂₃H₂₄FN₆Na₂O₉P_.6H₂O
Molecular Weight	732.51
PSA	205.76000
LogP	3.24120

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