CAS 901119-35-5|Fostamatinib (R788)
| Common Name | Fostamatinib (R788) | ||
|---|---|---|---|
| CAS Number | 901119-35-5 | Molecular Weight | 580.459 |
| Density | 1.5±0.1 g/cm3 | Boiling Point | 814.2±75.0 °C at 760 mmHg |
| Molecular Formula | C23H26FN6O9P | Melting Point | / |
| MSDS | / | Flash Point | 446.2±37.1 °C |
Names
| 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 |
|---|---|
| Synonym | More Synonyms |
Fostamatinib (R788) BiologicalActivity
| 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 >>SykResearch 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. |
Chemical & Physical Properties
| 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 |
| InChIKey | GKDRMWXFWHEQQT-UHFFFAOYSA-N |
| SMILES | COc1cc(Nc2ncc(F)c(Nc3ccc4c(n3)N(COP(=O)(O)O)C(=O)C(C)(C)O4)n2)cc(OC)c1OC |
| Storage condition | -20°C |
Synonyms
| Fostamatinib |
| R788 compound |
| Fostamatinib (R788) |
| R788 |
