R788(Fostamatinib disodium)

Uses

R 788 Sodium Salt is the sodium salt of R 788 which is a selective spleen tyrosine kinase (Syk) inhibitor. It may be used in the treatment of autoimmune diseases such as type 1 diabetes and has been tested in the treatment of rheumatoid athritis, leukemia and lymphoma.

Biological Activity

r788, which is the prodrug of r406, is a potnet and selective syk inhibitor. the spleen tyrosine kinase (syk) plays a key role in the signaling of activating fc receptors and the b-cell receptor (bcr).

in vitro

r406 was found to induce the apoptosis of the majority of examined dlbcl cell lines and could specifically inhibit both tonic- and ligand-induced bcr signaling (autophosphorylation of syk525/526 and sykdependent phosphorylation of the b-cell linker protein [blnk]) [1].

in vivo

r788 effectively inhibits bcr signaling, demonstrating reduced proliferation and survival of the malignant b cells and significantly prolonged survival of the treated eμ-tcl1 transgenic mouse. moreover, the effect of r788 was found to be selective for the malignant clones, since no disturbance in the production of normal b lymphocytes was observed [2].

target

Syk

References

[1] chen l, monti s, juszczynski p, daley j, chen w, witzig te, habermann tm, kutok jl, shipp ma. syk-dependent tonic b-cell receptor signaling is a rational treatment target in diffuse large b-cell lymphoma. blood. 2008 feb 15;111(4):2230-7.
[2] 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.
[3] bajpai m. fostamatinib, a syk inhibitor prodrug for the treatment of inflammatory diseases. idrugs. 2009 mar;12(3):174-85.