Fostamatinib

Fostamatinib (R788 disodium salt) is a prodrug of the active metabolite R406, which is a potent, ATP-competitive inhibitor of Syk kinase with Ki/IC50 of 30/41 nM; dose-dependently inhibits anti-IgE-mediated CHMC degranulation with an EC50 of 56 nM, inhibits all phosphorylation events downstream of Syk signaling; specifically inhibits FcγR signaling in human mast cells, macrophages, and neutrophils. R788 can inhibit local inflammatory injury mediated by immune complexes; reduces immune complex-mediated inflammation in arthritis models. Rheumatoid Arthritis Phase 3 Clinical (In Vivo) :Fostamatinib (R788) is highly bioavailable, and rapidly absorbed in Louvain rats. R406 following a single oral dose of R788 10 mg/kg or 20 mg/kg: AUC0-16 hrs= 10618 ng*h/mL and 30650 ng*h/mL respectively; Cmax=2600 ng/mL and 6500 ng/mL respectively (observed at 1 hour) ; t1/2=4.2 hours. The prodrug was not detected in plasma suggesting R788 is completely converted to R406.