TABLE 1

R406 specifically inhibits Syk-dependent FcR and BCR signaling

Inhibition by R406 was tested in a variety of Syk-dependent pathways in different cells. Each assay was optimized independently and run with appropriate controls.

Cell Type Stimulation Signaling Pathway Readout EC50 S.D.
μM
CHMC Anti-IgE FcϵRI Degranulation 0.056 0.02
CHMC Anti-IgE FcϵRI Leukotriene LTC4 0.093 0.076
CHMC Anti-IgE FcϵRI TNFα 0.118 0.031
CHMC Anti-IgE FcϵRI IL-8 0.140 0.016
CHMC Anti-IgE FcϵRI GM-CSF 0.158 0.025
CHMC Anti-IgG FcγR Degranulation 0.064 0.016
CHMC Anti-IgG FcγR Leukotriene LTC4 0.041 0.08
CHMC Anti-IgG FcγR TNFα 0.082 0.053
CHMC Anti-IgG FcγR IL-8 0.053 0.012
CHMC Anti-IgG FcγR GM-CSF 0.056 0.014
Monocytic line, THP-1 Anti-IgG FcγR TNFα 0.171 0.104
Primary human macrophages Anti-IgG FcγR TNFα 0.111 0.023
Primary human neutrophils Anti-IgG FcγR Oxidative burst 0.033 0.008
Primary human B-cells Anti-IgM BCR CD69 up-regulation 0.048 0.026