Fostamatinib sodium
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MedKoo CAT#: 200393

CAS#: 1025687-58-4 (sodium)

Description: Fostamatinib, also known as R 788 and R-935788, is an orally active, potent and selective Syk kinase inhibitor with potential anti-inflammatory and immunomodulating activities. Fostamatinib is also a pro-drug of R-406. 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.


Chemical Structure

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Fostamatinib sodium
CAS# 1025687-58-4 (sodium)

Theoretical Analysis

MedKoo Cat#: 200393
Name: Fostamatinib sodium
CAS#: 1025687-58-4 (sodium)
Chemical Formula: C23H24FN6Na2O9P
Exact Mass:
Molecular Weight: 624.42
Elemental Analysis: C, 44.24; H, 3.87; F, 3.04; N, 13.46; Na, 7.36; O, 23.06; P, 4.96

Price and Availability

Size Price Availability Quantity
25.0mg USD 150.0 Same day
50.0mg USD 250.0 Same day
100.0mg USD 450.0 Same day
200.0mg USD 750.0 Same day
500.0mg USD 1350.0 Same day
1.0g USD 2250.0 Same day
2.0g USD 3450.0 Same day
5.0g USD 4950.0 2 weeks
10.0g USD 7750.0 2 weeks
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Related CAS #: 1025687-58-4 (sodium)   901119-35-5 (free acid)   914295-16-2 (sodium hydrate)  

Synonym: R935788; R-935788; R 935788; R788; R 788; R-788 sodium. R935788 sodium. Fostamatinib sodium, Fostamatinib disodium hexahydrate; prodrug of R-406.

IUPAC/Chemical Name: sodium (6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)amino)-2,2-dimethyl-3-oxo-2H-pyrido[3,2-b][1,4]oxazin-4(3H)-yl)methyl phosphate

InChi Key: HSYBQXDGYCYSGA-UHFFFAOYSA-L

InChi Code: InChI=1S/C23H26FN6O9P.2Na/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);;/q;2*+1/p-2

SMILES Code: O=P([O-])([O-])OCN1C2=NC(NC3=NC(NC4=CC(OC)=C(OC)C(OC)=C4)=NC=C3F)=CC=C2OC(C)(C)C1=O.[Na+].[Na+]

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Fostamatinib disodium (R788, Tamatinib Fosdium), a prodrug of the active metabolite R406, is a Syk inhibitor with IC50 of 41 nM in a cell-free assay, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3.
In vitro activity: R406 is a competitive inhibitor for ATP binding to the Syk catalytic domain (Ki = 30 nM), and inhibits Syk kinase activity in vitro with an IC50 of 41 nM. Selectivity assessments using a panel of over 90 in vitro kinase assays showed that R406, whilst relatively specific for Syk, did demonstrate inhibitory activity on other kinases, including Flt3, Lyn (IC50 63 nM) and Lck (IC50 37 nM). When tested in cell-based assays, however, R406 inhibited all other kinases tested at 5- to 100-fold less potency than Syk as judged by phosphorylation of target proteins, despite the similar IC50 values on isolated kinase assays. Reference: Drugs Future. 2011;36(4):273. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284223/
In vivo activity: Fostamatinib (R788) has been shown to be highly active in two animal models of CLL - adoptively transferred T cell leukaemia 1 (TCL1) leukaemias and leukaemias that spontaneously develop in Emu-TCL1 transgenic mice. In addition, it has shown efficacy in murine models of non-Hodgkin’s lymphoma (NHL), reducing tumour burden and prolonging survival in treated mice. Notably, this effect was not seen in tumours lacking surface expression on the BCR, in keeping with the drugs proposed mechanism of action. The effects of Fostamatinib (as either R788 or R406) have been more extensively studied in vivo in a diverse range of animal models of allergy, autoimmunity and inflammation, where its inhibitory action on FcR-mediated signalling is thought to be the key mechanism of action. For example, treatment with Fostamatinib effectively prevents the development thrombocytopenia and haemolytic anaemia induced by the passive transfer of anti-platelet and anti-red cell antibodies respectively to mice. In rodent models of asthma, R406 reduced airway hyperresponsiveness (AHR) and markers of airway inflammation following antigen challenge in sensitized mice, in two distinct models. Similarly, in mice passively sensitised with anti-OVA IgE, R406 treatment prevented the development of AHR. Reference: Drugs Future. 2011;36(4):273. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284223/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 80.07
Water 3.0 4.8

Preparing Stock Solutions

The following data is based on the product molecular weight 624.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. doi: 10.1124/jpet.106.109058. Epub 2006 Aug 31. Erratum in: J Pharmacol Exp Ther. 2013 May;345(2):326. PMID: 16946104. 2. Buchner M, Fuchs S, Prinz G, Pfeifer D, Bartholomé K, Burger M, Chevalier N, Vallat L, Timmer J, Gribben JG, Jumaa H, Veelken H, Dierks C, Zirlik K. Spleen tyrosine kinase is overexpressed and represents a potential therapeutic target in chronic lymphocytic leukemia. Cancer Res. 2009 Jul 1;69(13):5424-32. doi: 10.1158/0008-5472.CAN-08-4252. Epub 2009 Jun 23. PMID: 19549911. 3. 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. doi: 10.1182/blood-2010-03-275180. Epub 2010 Aug 17. PMID: 20716772. 4. Young RM, Hardy IR, Clarke RL, Lundy N, Pine P, Turner BC, Potter TA, Refaeli Y. Mouse models of non-Hodgkin lymphoma reveal Syk as an important therapeutic target. Blood. 2009 Mar 12;113(11):2508-16. doi: 10.1182/blood-2008-05-158618. Epub 2008 Nov 3. PMID: 18981293; PMCID: PMC2947310.
In vitro protocol: 1. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. doi: 10.1124/jpet.106.109058. Epub 2006 Aug 31. Erratum in: J Pharmacol Exp Ther. 2013 May;345(2):326. PMID: 16946104. 2. Buchner M, Fuchs S, Prinz G, Pfeifer D, Bartholomé K, Burger M, Chevalier N, Vallat L, Timmer J, Gribben JG, Jumaa H, Veelken H, Dierks C, Zirlik K. Spleen tyrosine kinase is overexpressed and represents a potential therapeutic target in chronic lymphocytic leukemia. Cancer Res. 2009 Jul 1;69(13):5424-32. doi: 10.1158/0008-5472.CAN-08-4252. Epub 2009 Jun 23. PMID: 19549911.
In vivo protocol: 1. 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. doi: 10.1182/blood-2010-03-275180. Epub 2010 Aug 17. PMID: 20716772. 2. Young RM, Hardy IR, Clarke RL, Lundy N, Pine P, Turner BC, Potter TA, Refaeli Y. Mouse models of non-Hodgkin lymphoma reveal Syk as an important therapeutic target. Blood. 2009 Mar 12;113(11):2508-16. doi: 10.1182/blood-2008-05-158618. Epub 2008 Nov 3. PMID: 18981293; PMCID: PMC2947310.

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1: McBride A, Nayak P, Kreychman Y, Todd L, Duliege AM, Mehta AR. Fostamatinib disodium hexahydrate: a novel treatment for adult immune thrombocytopenia. Am J Manag Care. 2019 Nov;25(19 Suppl):S347-S358. PubMed PMID: 31809006.

2: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548340/ PubMed PMID: 31643662.

3: Kang Y, Jiang X, Qin D, Wang L, Yang J, Wu A, Huang F, Ye Y, Wu J. Efficacy and Safety of Multiple Dosages of Fostamatinib in Adult Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Front Pharmacol. 2019 Aug 14;10:897. doi: 10.3389/fphar.2019.00897. eCollection 2019. PubMed PMID: 31474860; PubMed Central PMCID: PMC6702340.

4: Hussar DA, Kludjian GA. Prucalopride succinate, Fostamatinib disodium hexahydrate, Avatrombopag maleate, and Lusutrombopag. J Am Pharm Assoc (2003). 2019 Jul - Aug;59(4):601-604. doi: 10.1016/j.japh.2019.05.013. PubMed PMID: 31296323.

5: Moore DC, Gebru T, Muslimani A. Fostamatinib for the treatment of immune thrombocytopenia in adults. Am J Health Syst Pharm. 2019 May 17;76(11):789-794. doi: 10.1093/ajhp/zxz052. PubMed PMID: 30951590.

6: Fostamatinib (Tavalisse) for ITP. Med Lett Drugs Ther. 2019 Feb 25;61(1566):28-30. PubMed PMID: 30845102.

7: Connell NT, Berliner N. Fostamatinib for the treatment of chronic immune thrombocytopenia. Blood. 2019 May 9;133(19):2027-2030. doi: 10.1182/blood-2018-11-852491. Epub 2019 Feb 25. Review. PubMed PMID: 30803989.

8: Bussel JB, Arnold DM, Boxer MA, Cooper N, Mayer J, Zayed H, Tong S, Duliege AM. Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program. Am J Hematol. 2019 May;94(5):546-553. doi: 10.1002/ajh.25444. Epub 2019 Mar 13. PubMed PMID: 30784097; PubMed Central PMCID: PMC6594140.

9: McKeage K, Lyseng-Williamson KA. Fostamatinib in chronic immune thrombocytopenia: a profile of its use in the USA. Drugs Ther Perspect. 2018;34(10):451-456. doi: 10.1007/s40267-018-0551-x. Epub 2018 Aug 29. Erratum in: Drugs Ther Perspect. 2018;34(12):594. PubMed PMID: 30459507; PubMed Central PMCID: PMC6223701.

10: Markham A. Fostamatinib: First Global Approval. Drugs. 2018 Jun;78(9):959-963. doi: 10.1007/s40265-018-0927-1. Review. PubMed PMID: 29869203.

11: Bussel J, Arnold DM, Grossbard E, Mayer J, Treliński J, Homenda W, Hellmann A, Windyga J, Sivcheva L, Khalafallah AA, Zaja F, Cooper N, Markovtsov V, Zayed H, Duliege AM. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018 Jul;93(7):921-930. doi: 10.1002/ajh.25125. Epub 2018 May 15. PubMed PMID: 29696684; PubMed Central PMCID: PMC6055608.

12: McKeage K, Lyseng-Williamson KA. Correction to: Fostamatinib in chronic immune thrombocytopenia: a profile of its use in the USA. Drugs Ther Perspect. 2018;34(12):594. doi: 10.1007/s40267-018-0575-2. Epub 2018 Nov 16. PubMed PMID: 31186610; PubMed Central PMCID: PMC6267526.

13: Newland A, Lee EJ, McDonald V, Bussel JB. Fostamatinib for persistent/chronic adult immune thrombocytopenia. Immunotherapy. 2018 Jan;10(1):9-25. doi: 10.2217/imt-2017-0097. Epub 2017 Oct 2. Review. PubMed PMID: 28967793.

14: Flanagan T, Martin P, Gillen M, Mathews D, Lisbon E, Kruusmägi M. Effects of ranitidine (antacid), food, and formulation on the pharmacokinetics of fostamatinib: results from five phase I clinical studies. Eur J Clin Pharmacol. 2017 Feb;73(2):185-195. doi: 10.1007/s00228-016-2156-4. Epub 2016 Nov 17. PubMed PMID: 27858108.

15: Martin P, Gillen M, Millson D, Oliver S, Brealey C, Surry D, Sweeny D, Lau D, Leese P. Effects of Fostamatinib on the Pharmacokinetics of the CYP2C8 Substrate Pioglitazone: Results From In Vitro and Phase 1 Clinical Studies. Clin Pharmacol Drug Dev. 2016 May;5(3):170-9. doi: 10.1002/cpdd.243. Epub 2016 Mar 23. PubMed PMID: 27163495.

16: Kunwar S, Devkota AR, Ghimire DK. Fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials. Rheumatol Int. 2016 Aug;36(8):1077-87. doi: 10.1007/s00296-016-3482-7. Epub 2016 Apr 25. PubMed PMID: 27113955.

17: Martin P, Gillen M, Ritter J, Mathews D, Brealey C, Surry D, Oliver S, Holmes V, Severin P, Elsby R. Effects of Fostamatinib on the Pharmacokinetics of Oral Contraceptive, Warfarin, and the Statins Rosuvastatin and Simvastatin: Results From Phase I Clinical Studies. Drugs R D. 2016 Mar;16(1):93-107. doi: 10.1007/s40268-015-0120-x. PubMed PMID: 26748647; PubMed Central PMCID: PMC4767723.

18: Martin P, Gillen M, Millson D, Oliver S, Brealey C, Grossbard EB, Baluom M, Lau D, Sweeny D, Mant T, Craven K. Effects of CYP3A4 Inhibitors Ketoconazole and Verapamil and the CYP3A4 Inducer Rifampicin on the Pharmacokinetic Parameters of Fostamatinib: Results from In Vitro and Phase I Clinical Studies. Drugs R D. 2016 Mar;16(1):81-92. doi: 10.1007/s40268-015-0118-4. PubMed PMID: 26739683; PubMed Central PMCID: PMC4767720.

19: Flinn IW, Bartlett NL, Blum KA, Ardeshna KM, LaCasce AS, Flowers CR, Shustov AR, Thress KS, Mitchell P, Zheng F, Skolnik JM, Friedberg JW. A phase II trial to evaluate the efficacy of fostamatinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Eur J Cancer. 2016 Feb;54:11-17. doi: 10.1016/j.ejca.2015.10.005. Epub 2015 Dec 18. PubMed PMID: 26707592.

20: Martin P, Oliver S, Gillen M, Marbury T, Millson D. Pharmacokinetic Properties of Fostamatinib in Patients With Renal or Hepatic Impairment: Results From 2 Phase I Clinical Studies. Clin Ther. 2015 Dec 1;37(12):2823-36. doi: 10.1016/j.clinthera.2015.09.016. Epub 2015 Oct 27. PubMed PMID: 26519231.



Additional Information

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).