fostamatinib   Click here for help

GtoPdb Ligand ID: 7796

Synonyms: R 788 | R-788 | R7935788 | Tavalisse® | Tavlesse®
Approved drug PDB Ligand Immunopharmacology Ligand
fostamatinib is an approved drug (FDA (2018), EMA (2020))
Compound class: Synthetic organic
Comment: Fostamatinib is a spleen tyrosine kinase (Syk) inhibitor prodrug. Fostamatinib is administered orally in disodium salt preparations (e.g. PubChem CID 25008120 and fostamatinib disodium hexahydrate CID 24828759). It is rapidly converted to tamatinib by alkaline phosphatases in intestinal enterocytes [6]. Although development in rheumatoid arthritis was discontinued in 2013 due to a lack of observed efficacy, development continued in patients with chronic and persistent immune thrombocytopenia (ITP).
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 11
Hydrogen bond donors 4
Rotatable bonds 10
Topological polar surface area 196.53
Molecular weight 580.15
XLogP 1.06
No. Lipinski's rules broken 1
Click here for help
Canonical SMILES COc1cc(Nc2ncc(c(n2)Nc2ccc3c(n2)N(COP(=O)(O)O)C(=O)C(O3)(C)C)F)cc(c1OC)OC
Isomeric SMILES COc1cc(Nc2ncc(c(n2)Nc2ccc3c(n2)N(COP(=O)(O)O)C(=O)C(O3)(C)C)F)cc(c1OC)OC
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)
1. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C et al.. (2006)
R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation.
J Pharmacol Exp Ther, 319 (3): 998-1008. [PMID:16946104]
2. Kunwar S, Devkota AR, Ghimire DK. (2016)
Fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials.
Rheumatol Int, 36 (8): 1077-87. [PMID:27113955]
3. Maringwa J, Kågedal M, Hamrén UW, Martin P, Cox E, Hamrén B. (2015)
Pharmacokinetic-pharmacodynamic modeling of fostamatinib efficacy on ACR20 to support dose selection in patients with rheumatoid arthritis (RA).
J Clin Pharmacol, 55 (3): 328-35. [PMID:25280085]
4. Newland A, Lee EJ, McDonald V, Bussel JB. (2018)
Fostamatinib for persistent/chronic adult immune thrombocytopenia.
Immunotherapy, 10 (1): 9-25. [PMID:28967793]
5. Niscola P, Scaramucci L, Giovannini M. (2018)
Spleen tyrosine kinase inhibition: a new promising approach to chronic and refractory immune thrombocytopenia.
Immunotherapy, 10 (1): 5-7. [PMID:29192558]
6. Sweeny DJ, Li W, Clough J, Bhamidipati S, Singh R, Park G, Baluom M, Grossbard E, Lau DT. (2010)
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, 38 (7): 1166-76. [PMID:20371637]