1140525-25-2

SB 290157, functions as a competitive antagonist of ¹²⁵ I-C3a radioligand binding to rat basophilic leukemia-2H3 cells expressing the human C3aR (RBL-C3aR), with an IC ₅₀ of 200 nM. SB 290157 blocks C3a-induced C3aR internalization in a concentration-dependent manner and C3a-induced Ca ²⁺ mobilization in RBL-C3aR cells and human neutrophils with IC ₅₀ s f 27.7 and 28 nM, respectively. SB 290157 is selective for the C3aR in that it does not antagonize the C5aR or six other chemotactic G protein-coupled receptors. SB 290157 also inhibits C3a-induced Ca ²⁺ mobilization of RBL-2H3 cells expressing the mouse and guinea pig C3aRs. It potently inhibits C3a-mediated ATP release from guinea pig platelets and inhibits C3a-induced potentiation of the contractile response to field stimulation of perfused rat caudal artery.

SB 290157, inhibits neutrophil recruitment in a guinea pig LPS-induced airway neutrophilia model and decreases paw edema in a rat adjuvant-induced arthritis model. The antagonist is able to reduce joint swelling only at 3 h, and about 50% inhibition of joint swelling is observed with the concentration of 30 mg/kg. The C3 level is significantly decreased at 3 h compared with naive mice showing complement consumption. Furthermore, the C3 activation is observed and increased corresponding to the graded concentration of anti-OVA pAb.