During extended incubation in whole blood, E5564 retained activity better than similar concentrations of the first-generation antagonist E5531. Based on the proposed mechanism of action as a cell surface antagonist, it is likely that E5564 can completely block cellular activation by LPS. This block is achieved by concentrations of E5564 as low as 10 nM (14 ng/ml) in vitro, and at doses of 1 mg/kg or less in animal models challenged with lethal LPS doses.