Fostamatinib

Fostamatinib
	; Fostamatinib
	; Fostamatinib disodium
Names
	IUPAC name [6-({5-Fluoro-2-[(3,4,5-trimethoxyphenyl)amino]pyrimidin-4-yl}amino)-2,2-dimethyl-3-oxo-2,3-dihydro-4H-pyrido[3,2-b][1,4]oxazin-4-yl]methyl dihydrogen phosphate
	Other names Tamatinib fosdium; R-788; NSC-745942; R-935788
Identifiers
CAS Number	901119-35-5 ; 1025687-58-4 (fostamatinib disodium) ;
3D model (JSmol)	Interactive image;
ChemSpider	9846198;
ECHA InfoCard	100.125.771
PubChem CID	11671467; 25008120 (fostamatinib disodium);
UNII	SQ8A3S5101;
CompTox Dashboard (EPA)	DTXSID401009170 ;
	InChI InChI=1S/C23H26FN6O9P/c1-23(2)21(31)30(11-38-40(32,33)34)20-14(39-23)6-7-17(28-20)27-19-13(24)10-25-22(29-19)26-12-8-15(35-3)18(37-5)16(9-12)36-4/h6-10H,11H2,1-5H3,(H2,32,33,34)(H2,25,26,27,28,29);
	SMILES Fc1cnc(nc1Nc2nc3N(C(=O)C(Oc3cc2)(C)C)COP(=O)(O)O)Nc4cc(OC)c(OC)c(OC)c4;
Properties
Chemical formula	C23H26FN6O9P
Molar mass	580.466 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Fostamatinib is an experimental drug candidate for the treatment of a variety of diseases, originally developed by Rigel Pharmaceuticals. The drug is administered orally as a disodium salt, and is a prodrug of the active compound tamatinib (R-406),^[1] which is an inhibitor of the enzyme spleen tyrosine kinase (Syk).^[2]

Fostamatinib has been in phase II trials for rheumatoid arthritis, autoimmune thrombocytopenia and lymphoma.^[1]^[3]

A phase II study of rheumatoid arthritis patients failing to respond to a biologic agent showed little efficacy as compared to placebo, but the drug was well tolerated. In patients with high inflammatory burden, measured by levels of C-reactive protein, ACR20 was achieved by a significantly higher portion of those in the fostamatinib group (42%) versus the placebo group (26%).^[4]

On June 4, 2013, Astra Zeneca announced they were giving up future development on the compound, and terminated their license with Rigel after early results from a Phase IIb study for rheumatoid arthritis. Astra Zeneca is estimated to lose $140 million as part of the contract termination.^[5] Rigel plans to now focus on ITP and start phase III clinical trials soon.

External links

Rigel Pharmaceuticals http://www.rigel.com/rigel/ITP

References

^ ^a ^b S.P. McAdoo and F.W.K. Tam (2011). "Fostamatinib Disodium". Drugs of the Future. 36 (4): 273–280.
^ Braselmann, S; Taylor, V; Zhao, H; Wang, S; Sylvain, C; Baluom, M; Qu, K; Herlaar, E; Lau, A (2006). "R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation". The Journal of Pharmacology and Experimental Therapeutics. 319 (3): 998–1008. doi:10.1124/jpet.106.109058. PMID 16946104.
^ Morales-Torres, Jorge (2010). "R788 (fostamatinib disodium): a novel approach for the treatment of rheumatoid arthritis". International Journal of Clinical Rheumatology. 5 (1): 9–15. doi:10.2217/ijr.09.69.
^ "Fostamatinib Shown to Be Safe but Not Effective in Rheumatoid Arthritis Patients Unresponsive to Biologic Agents". Science Daily. Jan 27, 2011. Retrieved Dec 13, 2012.
^ Rigel to cut 30 jobs, focus on three drug programs, Sept 5th 2013, http://www.bizjournals.com/sanfrancisco/blog/biotech/2013/09/rigel-fostamatinib-itp-rigl-layoffs.html

[dotf-1] S.P. McAdoo and F.W.K. Tam (2011). "Fostamatinib Disodium". Drugs of the Future. 36 (4): 273–280.

[2] Braselmann, S; Taylor, V; Zhao, H; Wang, S; Sylvain, C; Baluom, M; Qu, K; Herlaar, E; Lau, A (2006). "R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation". The Journal of Pharmacology and Experimental Therapeutics. 319 (3): 998–1008. doi:10.1124/jpet.106.109058. PMID 16946104.

[3] Morales-Torres, Jorge (2010). "R788 (fostamatinib disodium): a novel approach for the treatment of rheumatoid arthritis". International Journal of Clinical Rheumatology. 5 (1): 9–15. doi:10.2217/ijr.09.69.

[4] "Fostamatinib Shown to Be Safe but Not Effective in Rheumatoid Arthritis Patients Unresponsive to Biologic Agents". Science Daily. Jan 27, 2011. Retrieved Dec 13, 2012.

[5] Rigel to cut 30 jobs, focus on three drug programs, Sept 5th 2013, http://www.bizjournals.com/sanfrancisco/blog/biotech/2013/09/rigel-fostamatinib-itp-rigl-layoffs.html

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