SB 290157 (trifluoroacetate salt)

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).