W-54011 is a potent non-peptide C5a receptor antagonist. W-54011 inhibits the binding of 125I-labeled C5a to human neutrophils (Ki = 2.2 nM). W-54011 inhibits C5a-induced intracellular Ca2+ mobilization, chemotaxis, and generation of ROS in human neutrophils (IC50s = 3.1 nM, 2.7 nM, and 1.6 nM, respectively).

C5aR:2.2 nM(Ki), ROS:1.6 nM(ki), Ca2+ mobilization: 3.1 nM, Chemotaxis:2.7 nM(ki)

W-54011 does not show agonistic activity at up to 10 μM and shifts rightward the concentration-response curves to C5a without depressing the maximal responses, showing that W-54011 is a full antagonist. At concentrations up to 10 μM, W-54011 does not affect Ca2+ mobilization stimulated with sub-maximally effective concentrations of fMLP (1 nM), platelet-activating factor (0.3 nM), and IL-8 (0.1 nM)[1].

W-54011 is able to inhibit the response in cynomolgus monkeys and gerbils (IC50 = 1.7 nM and 3.2 nM, respectively). In Male mongolian gerbils injected with rhC5a, W-54011 (3-30 mg/kg; oral; for 4 hours) inhibited C5a-induced neutropenia in a dose-dependent manner in gerbils. The species selectivity of W-54011 is examined in rhC5a-induced intracellular Ca2+ mobilization of neutrophils in various species [1].