Background:

W 54011 is a potent and orally active non-peptide C5a receptor antagonist with Ki value of 2.2 nM [1].

The complement C5a is a 74-amino acid peptide produced during complement activation processes. C5a plays an important role in mast cell degranulation, smooth muscle contraction, monocyte migration, blood vessel dilatation, increased vascular permeability at in?ammatory sites , and recruitment of immune cells [1][2].

W 54011 is a potent and orally active C5a receptor antagonist. W 54011 inhibited the binding of 125I-labeled C5a to human neutrophils with Ki value of 2.2 nM. In human neutrophils, W 54011 inhibited C5a-induced chemotaxis, intracellular Ca2+ mobilization, and generation of reactive super oxide species with IC50 values of 2.7, 3.1, and 1.6 nM, respectively. W 54011 was species specific and was able to inhibit C5a-induced intracellular Ca2+ mobilization in neutrophils of cynomolgus monkeys and gerbils but not mice, rats, guinea pigs, rabbits, and dogs [1]. In HMEC-1 endothelial cell line, W 54011 signi?cantly inhibited C5a-induced proliferation and cell cycle progression in a dose-dependent way. W 54011 also inhibited the proliferative effects of 10 nM C5a and dose-dependently inhibited the formation of ring-shaped structures induced by C5a [2].

In gerbils, oral administration of W-54011 (3-30 mg/kg) dose-dependently inhibited C5a-induced neutropenia [1].

参考文献:
[1].Sumichika H, Sakata K, Sato N, et al.? Identification of a potent and orally active non-peptide C5a receptor antagonist. J Biol Chem. 2002 Dec 20;277(51):49403-7.
[2].Kurihara R, Yamaoka K, Sawamukai N, et al.? C5a promotes migration, proliferation, and vessel formation in endothelial cells. Inflamm Res. 2010 Aug;59(8):659-66.