Description
W-54011 is an orally bioavailable, nonpeptide antagonist of complement component 5a receptor 1 (C5aR), also known as cluster of differentiation 88 (CD88). W-54011 inhibits
125I-rhC5a binding in neutrophils (K
i = 2.2 nM) and C5a-mediated intracellular Ca
2+ mobilization (IC
50 = 3.1 nM). W-54011 is selective and does not affect Ca
2+ mobilization mediated by other G protein-coupled receptor (GPCR) ligands, N-Formyl-Met-Leu-Phe (fMLF; ), or IL-8 up to a concentration of 10 μM. It inhibits Ca
2+ mobilization in neutrophils in humans, cynomolgus monkeys, and gerbils, but not in mice, rats, guinea pigs, rabbits, or dogs. At 10 nM, W-54011 also inhibits C5a-mediated migration and vessel formation of human microvascular endothelial cells (HMEC-1).
in vivo
W-54011 (3-30 mg/kg; oral administration; for 4 hours; male mongolian gerbils) treatment inhibited C5a-induced neutropenia in a dose-dependent manner in gerbils[1].
The species selectivity of W-54011 is examined in rhC5a-induced intracellular Ca2+ mobilization of neutrophils in various species. The W-54011 is able to inhibit the response in cynomolgus monkeys and gerbils with IC50 values of 1.7 nM and 3.2 nM, respectively, but not in mice, rats, guinea pigs, rabbits, and dogs[1].
| Animal Model: | Male mongolian gerbils (6-12 weeks) injected with rhC5a[1] |
| Dosage: | 3 mg/kg, 10 mg/kg, 30 mg/kg |
| Administration: | Oral administration; for 4 hours |
| Result: | Inhibited C5a-induced neutropenia in a dose-dependent manner. |
References
[1] HIROSHI SUMICHIKA. Identification of a potent and orally active non-peptide C5a receptor antagonist.[J]. The Journal of Biological Chemistry, 2002, 277 51: 49403-49407. DOI:
10.1074/jbc.m209672200[2] RYUJI KURIHARA. C5a promotes migration, proliferation, and vessel formation in endothelial cells.[J]. Inflammation Research, 2010, 59 8: 659-666. DOI:
10.1007/s00011-010-0178-4
![N-[[4-(Dimethylamino)phenyl]methyl]-1,2,3,4-tetrahydro-7-methoxy-N-[4-(1-methylethyl)phenyl]-1-naphthalenecarboxamide hydrochloride Structure](https://www.chemicalbook.com/CAS/GIF/405098-33-1.gif)
