fostamatinib   

GtoPdb Ligand ID: 7796

Synonyms: R 788 | R-788 | R7935788 | Tavalisse®
fostamatinib is an approved drug (FDA (2018))
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).
2D Structure
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Physico-chemical Properties
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
SMILES / InChI / InChIKey
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)
InChI Key GKDRMWXFWHEQQT-UHFFFAOYSA-N
No information available.
Summary of Clinical Use
Fostamatinib (as the disodium hexahydrate salt) received FDA approval for the treatment of chronic immune thrombocytopenia (ITP) [5] in April 2018, in particular for the treatment of patients with an inadequete response to previous treatment.
Fostamatinib has completed Phase 3 clinical trials for rheumatoid arthritis [3] (NCT01197534 & NCT01197755), and Phase 2 for a range of solid tumours (NCT00923481).
Mechanism Of Action and Pharmacodynamic Effects
The active moeity, tamatinib inhibits Syk kinase-mediated IgE- and IgG-mediated activation of Fc gamma receptor signaling, resulting in inhibition of the activation of mast cells, macrophages, and B-cells and related inflammatory responses and tissue damage [1,4].