R406 (free base)

R406 free base is an orally available and competitive Syk/FLT3 inhibitor for ATP binding with a K_i of 30 nM, potently inhibits Syk kinase activity in vitro with an IC₅₀ of 41 nM, measured at an ATP concentration corresponding to its K_m value. R406 free base reduces immune complex-mediated inflammation^[1]. R406 free base also inhibits Lyn (IC₅₀=63 nM) and Lck (IC₅₀=37 nM)^[2]. IC50 & Target: Ki: 30 nM (Syk)^[1]
IC50: 41 nM (Syk)^[1]
FLT3^[1]
IC50: 63 nM (Lyn), 37 nM (Lck)^[2] In Vitro: R406 inhibits adenosine A3 receptor (IC₅₀=0.081 µM), adenosine transporter (IC₅₀=1.84 µM), and monoamine transporter (IC₅₀=2.74 µM)^[1].
R406 inhibits Huh7 hepatocyte, A549 epithelial, and H1299 lung cancer lines with EC₅₀s of 15.1, 2.9 and 6.3 µM, respectively^[1].
R406 inhibits phosphorylation of Syk substrate LAT in mast cells and BLNK/SLP65 in B cells^[1]. In Vivo: R406 (5 and 10 mg/kg) shows efficacy in the amelioration of the Arthus reaction and in reducing clinical symptoms in the collagen antibody-induced arthritis (CAIA) and K/BxN models of rheumatoid arthritis (RA). Immune complex (IC)-mediated inflammation is reduced by inhibition of Fc receptor signaling with R406^[1].