901119-35-5

901119-35-5 structure

Name: Fostamatinib (R788)
Chemical Name: [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 dihydrogen phosphate
CAS Number: 901119-35-5
Molecular Formula: C₂₃H₂₆FN₆O₉P
Molecular Weight: 580.459
Catalog: Biochemical Inhibitor Angiogenesis Syk inhibitor
Create Date: 2018-07-31 10:40:01
Modify Date: 2024-01-04 18:20:21
Fostamatinib (R788), a prodrug of the active metabolite R406, is a potent Syk inhibitor with IC50 of 41 nM.

Name	[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 dihydrogen phosphate
Synonyms	Fostamatinib R788 compound Fostamatinib (R788) R788

Description	Fostamatinib (R788), 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. [4]. Sprissler C, et al. Depletion of STAT5 blocks TEL-SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice. Blood Cancer J. 2014 Aug 22;4:e240. [5]. Puissant A, et al. SYK is a critical regulator of FLT3 in acute myeloid leukemia. Cancer Cell. 2014 Feb 10;25(2):226-42. [6]. Okubo K, et al. Macrophage extracellular trap formation promoted by platelet activation is a key mediator of rhabdomyolysis-induced acute kidney injury. Nat Med. 2018 Feb;24(2):232-238.

Density	1.5±0.1 g/cm3
Boiling Point	814.2±75.0 °C at 760 mmHg
Molecular Formula	C₂₃H₂₆FN₆O₉P
Molecular Weight	580.459
Flash Point	446.2±37.1 °C
Exact Mass	580.148315
PSA	199.76000
LogP	2.12
Vapour Pressure	0.0±3.1 mmHg at 25°C
Index of Refraction	1.629
Storage condition	-20°C

901119-38-8

~50%

901119-35-5

Literature: RIGEL PHARMACEUTICALS, INC. Patent: WO2008/64274 A1, 2008 ; Location in patent: Page/Page column 94 ;

901119-35-5	1025687-58-4
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