R788 is an orally-available, ATP-competitive, methylene phosphate prodrug of R406, which is a potent inhibitor of Syk (IC50 = 41 nM). [1] In a broad panel of receptor, ion channel, and enzyme binding assays, R406 was shown to inhibit adenosine A3 receptor (IC50 = 81 nM), adenosine transporter (IC50 = 1.8 uM), and monoamine transporter (IC50 = 2.7 uM). Followup measurements for ligand-induced guanosine 5'-O-(thiotriphosphate) binding to the adenosine A3 receptor showed that R406 possesses antagonistic activity with an IC50 of 93 nM. R406 inhibits phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 does not inhibit phosphorylation of Sky tyrosine 352, but does inhibit phosphorylation of LAT tyrosine 191. R406 also inhibits IgE- and IgG-mediated activation of Fc receptor signaling.

In a large panel of diffuse large B-cell lymphoma cell lines, R406 inhibited cellular proliferation at EC50s ranging from 0.8 to 8.1 uM. [2]