Fostamatinib sodium

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WARNING: This product is for research use only, not for human or veterinary use.

Description:Fostamatinib, also known as R 788 andR-935788, is an orallyactive, 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.

Price and Availability

Fostamatinib sodium, purity > 98%, is in stock.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200393Name: Fostamatinib sodiumCAS#: 1025687-58-4 (sodium)Chemical Formula: C23H24FN6Na2O9PExact Mass: Molecular Weight: 624.42Elemental Analysis:C, 44.24; H, 3.87; F, 3.04; N, 13.46; Na, 7.36; O, 23.06; P, 4.96

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+]

Technical Data

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).  

References

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 RheumatoidArthritis: 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 ofranitidine (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. PubMedPMID: 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 SubstratePioglitazone: Results From In Vitro and Phase 1 Clinical Studies. Clin PharmacolDrug 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 andVerapamil and the CYP3A4 Inducer Rifampicin on the Pharmacokinetic Parameters ofFostamatinib: 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, ShustovAR, 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: ResultsFrom 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.