Animal experiment:

Rats: SB 290157 is administered b.i.d. at 30, 10, and 3 mg/kg i.p. in a final volume of 0.5 mL starting on the day of adjuvant injection. Cages are modified to allow the compromised animals free access to food and water. Control animals are given vehicle alone. Change in paw volume is presented as mean and SEM of 10-12 animals/group, and the percentage inhibition of hind paw edema is calculated[1]. Mice: Administration of SB 290157, a C3aR antagonist, (10 or 30 mg/kg) is injected i.p. two times, at 0 (right after OVA injection) and 2 h while 5% ethanol in PBS is used as a vehicle control. Joint swelling is measured using a dial thickness gauge before injection, at 0.5 h, and then every hour until 5 h after OVA injection[2].

IC50: 200 nM

SB 290157 is a C3aR antagonist.

The anaphylatoxin C3a, a potent chemotactic peptide and inflammatory mediator, binds to and activates a G-protein-coupled receptor. Molecular cloning of the C3aR has facilitated the identification of the non-peptide C3aR antagonists.

In vitro: SB 290157 was a competitive antagonist of 125I-C3a and binding to rat basophilic leukemia (RBL)-2H3 cells expressing the human C3aR , with an IC50 of 200 nM. SB 290157 could also block the C3a-induced C3aR internalization concentration-dependently and C3a-induced Ca21 mobilization in RBL-C3aR cells and human neutrophils. SB 290157 was founf to be selective for the C3aR in that it did not antagonize the C5aR or six other chemotactic G protein-coupled receptors. In addition, SB 290157 could also inhibit C3a induced Ca21 mobilization of RBL-2H3 cells expressing the mouse and guinea pig C3aRs [1].

In vivo: In animal models, SB 290157 was able to inhibit neutrophil recruitment in a guinea pig LPS-induced airway neutrophilia model and decrease paw edema in a rat adjuvant-induced arthritis model [1].

Clinical trial: So far, no clinical study has been conducted.

Reference:
[1] R.  S. Ames, D. Lee, J. J. Foley, et al. Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a receptor that demonstrates antiinflammatory activity in animal models. Journal of Immunology 166(10), 6341-6348 (2001).