MedKoo product information:

Fostamatinib

Description of Fostamatinib:  Fostamatinib disodium is an orally available disodium salt of the Syk kinase inhibitor fostamatinib with potential anti-inflammatory and immunomodulating activities. Fostamatinib inhibits Syk kinase-mediated IgG Fc gamma receptor signaling, resulting in inhibition of the activation of mast cells, macrophages, and B-cells and related inflammatory responses and tissue damage. Syk kinase, widely expressed in hematopoietic cells, is a nonreceptor tyrosine kinase that is involved in coupling activated immunoreceptors to signal downstream events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:    AstraZeneca and Rigel Pharmaceuticals.

Fostamatinib is an experimental drug candidate for the treatment of a variety of diseases. It is in Phase III clinical trials for rheumatoid arthritis and Phase II trials for autoimmune thrombocytopenia and lymphoma.  The oral drug is used as its disodium salt and it is a prodrug of the active compound tamatinib (R-406), which is an inhibitor of the enzyme spleen tyrosine kinase (Syk) (source: http://en.wikipedia.org/wiki/Fostamatinib).

Fostamatinib proven to be safe but not effective:  See Public release date: 27-Jan-2011:

1: Genovese MC, Kavanaugh A, Weinblatt ME, Peterfy C, Dicarlo J, White ML, O'Brien M, Grossbard EB, Magilavy DB. An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: A three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents. Arthritis Rheum. 2011 Feb;63(2):337-45. doi: 10.1002/art.30114. PubMed PMID: 21279990.

2: Witzig TE, Gupta M. Signal transduction inhibitor therapy for lymphoma. Hematology Am Soc Hematol Educ Program. 2010;2010:265-70. PubMed PMID: 21239804.

3: Baluom M, Samara E, Grossbard EB, Lau DT. Fostamatinib, a Syk-Kinase Inhibitor, Does Not Affect Methotrexate Pharmacokinetics in Patients With Rheumatoid Arthritis. J Clin Pharmacol. 2011 Jan 5. [Epub ahead of print] PubMed PMID: 21209239.

4: Otón T, Silva-Fernández L, Andreu JL. Spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis. N Engl J Med. 2011 Jan 6;364(1):83; author reply 84. PubMed PMID: 21208114.

5: Okamoto H, Kobayashi A. Spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis. N Engl J Med. 2011 Jan 6;364(1):83-4; author reply 84. PubMed PMID: 21208113.

6: Genovese MC, Kavanaugh A, Weinblatt ME, Peterfy C, Dicarlo J, White ML, O-Brien M, Grossbard EB, Magilavy DB. An oral syk kinase inhibitor in the treatment of rheumatoid arthritis: A 3 month randomized placebo controlled phase 2 study in patients with active RA who had failed biologic agents. Arthritis Rheum. 2010 Oct 27. [Epub ahead of print] PubMed PMID: 20981820.

7: Rivera J, Colbert RA. Healing the Syk through kinase inhibitors. N Engl J Med. 2010 Sep 30;363(14):1362-4. PubMed PMID: 20879886.

8: Weinblatt ME, Kavanaugh A, Genovese MC, Musser TK, Grossbard EB, Magilavy DB. An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis. N Engl J Med. 2010 Sep 30;363(14):1303-12. PubMed PMID: 20879879.

9: Suljagic M, Longo PG, Bennardo S, Perlas E, Leone G, Laurenti L, Efremov DG. The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Eμ- TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling. Blood. 2010 Dec 2;116(23):4894-905. Epub 2010 Aug 17. PubMed PMID: 20716772.

10: Colonna L, Catalano G, Chew C, D'Agati V, Thomas JW, Wong FS, Schmitz J, Masuda ES, Reizis B, Tarakhovsky A, Clynes R. Therapeutic targeting of Syk in autoimmune diabetes. J Immunol. 2010 Aug 1;185(3):1532-43. Epub 2010 Jul 2. PubMed PMID: 20601600; PubMed Central PMCID: PMC2981095.

11: Pamuk ON, Lapchak PH, Rani P, Pine P, Dalle Lucca JJ, Tsokos GC. Spleen tyrosine kinase inhibition prevents tissue damage after ischemia-reperfusion. Am J Physiol Gastrointest Liver Physiol. 2010 Aug;299(2):G391-9. Epub 2010 Jun 3. PubMed PMID: 20522642.

12: Lin TS. New agents in chronic lymphocytic leukemia. Curr Hematol Malig Rep. 2010 Jan;5(1):29-34. Review. PubMed PMID: 20425394.

13: Sweeny DJ, Li W, Grossbard E, Lau DT. Contribution of gut bacteria to the metabolism of the spleen tyrosine kinase (Syk) inhibitor R406 in cynomolgus monkey. Xenobiotica. 2010 Jun;40(6):415-23. PubMed PMID: 20415544.

14: Sweeny DJ, Li W, Clough J, Bhamidipati S, Singh R, Park G, Baluom M, Grossbard E, Lau DT. Metabolism of fostamatinib, the oral methylene phosphate prodrug of the spleen tyrosine kinase inhibitor R406 in humans: contribution of hepatic and gut bacterial processes to the overall biotransformation. Drug Metab Dispos. 2010 Jul;38(7):1166-76. Epub 2010 Apr 6. PubMed PMID: 20371637.

15: Opar A. Kinase inhibitors attract attention as oral rheumatoid arthritis drugs. Nat Rev Drug Discov. 2010 Apr;9(4):257-8. PubMed PMID: 20357793.

16: Deng GM, Liu L, Bahjat FR, Pine PR, Tsokos GC. Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus-prone mice. Arthritis Rheum. 2010 Jul;62(7):2086-92. PubMed PMID: 20222110; PubMed Central PMCID: PMC2902591.

17: Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, Lacasce A, Schaefer-Cutillo J, De Vos S, Sinha R, Leonard JP, Cripe LD, Gregory SA, Sterba MP, Lowe AM, Levy R, Shipp MA. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010 Apr 1;115(13):2578-85. Epub 2009 Nov 17. PubMed PMID: 19965662; PubMed Central PMCID: PMC2852362.

18: Smith J, McDaid JP, Bhangal G, Chawanasuntorapoj R, Masuda ES, Cook HT, Pusey CD, Tam FW. A spleen tyrosine kinase inhibitor reduces the severity of established glomerulonephritis. J Am Soc Nephrol. 2010 Feb;21(2):231-6. Epub 2009 Dec 3. PubMed PMID: 19959716; PubMed Central PMCID: PMC2834545.

19: Hahn CK, Berchuck JE, Ross KN, Kakoza RM, Clauser K, Schinzel AC, Ross L, Galinsky I, Davis TN, Silver SJ, Root DE, Stone RM, DeAngelo DJ, Carroll M, Hahn WC, Carr SA, Golub TR, Kung AL, Stegmaier K. Proteomic and genetic approaches identify Syk as an AML target. Cancer Cell. 2009 Oct 6;16(4):281-94. PubMed PMID: 19800574; PubMed Central PMCID: PMC2803063.

20: Downing JR. Can treating the SYK cell cure leukemia? Cancer Cell. 2009 Oct 6;16(4):270-1. PubMed PMID: 19800569.

21: Sanderson MP, Lau CW, Schnapp A, Chow CW. Syk: a novel target for treatment of inflammation in lung disease. Inflamm Allergy Drug Targets. 2009 Jun;8(2):87-95. Review. PubMed PMID: 19530990.

22: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Jan-Feb;31(1):47-57. PubMed PMID: 19357798.

23: Bajpai M. Fostamatinib, a Syk inhibitor prodrug for the treatment of inflammatory diseases. IDrugs. 2009 Mar;12(3):174-85. PubMed PMID: 19333898.

24: Clemens GR, Schroeder RE, Magness SH, Weaver EV, Lech JW, Taylor VC, Masuda ES, Baluom M, Grossbard EB. Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing. Birth Defects Res A Clin Mol Teratol. 2009 Feb;85(2):130-6. PubMed PMID: 19107952.

25: Podolanczuk A, Lazarus AH, Crow AR, Grossbard E, Bussel JB. Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood. 2009 Apr 2;113(14):3154-60. Epub 2008 Dec 18. PubMed PMID: 19096013.

26: Weinblatt ME, Kavanaugh A, Burgos-Vargas R, Dikranian AH, Medrano-Ramirez G, Morales-Torres JL, Murphy FT, Musser TK, Straniero N, Vicente-Gonzales AV, Grossbard E. Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-week, randomized, placebo-controlled trial. Arthritis Rheum. 2008 Nov;58(11):3309-18. PubMed PMID: 18975322.

27: Bahjat FR, Pine PR, Reitsma A, Cassafer G, Baluom M, Grillo S, Chang B, Zhao FF, Payan DG, Grossbard EB, Daikh DI. An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupus. Arthritis Rheum. 2008 May;58(5):1433-44. PubMed PMID: 18438845.

28: Sheridan C. Small molecule challenges dominance of TNF-alpha inhibitors. Nat Biotechnol. 2008 Feb;26(2):143-4. PubMed PMID: 18259158.

29: Pine PR, Chang B, Schoettler N, Banquerigo ML, Wang S, Lau A, Zhao F, Grossbard EB, Payan DG, Brahn E. Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor. Clin Immunol. 2007 Sep;124(3):244-57. Epub 2007 May 29. PubMed PMID: 17537677.