SB 290157 (trifluoroacetate salt)

SB 290157 (trifluoroacetate salt) is used as a selective nonpeptide C3aR antagonist. SB 290157 was a selective antagonist for rat basophilic leukemia cells expressing the human C3aR (IC50 of 200 nM). Antagonism by SB 290157 was not only limited to the human C3aR (IC50 of 12 nM), it also inhibited C3a-induced Ca2+ mobilization of cells expressing the mouse and guinea-pig C3aR (IC50 of 7 and 30 nM, respectively). ^[1].

SB 290157 (trifluoroacetate salt) (0.1 µM) significantly increased the abundance of SM22α mRNA and decreased the abundance of osteopontin mRNA in VSMCs from SHR rats, but these did not occur in cells from WKY rats ^[2]. C3a overexpression markedly altered the distribution of vinculin in human podocyte line cells, C3aR inhibition with 1 µM SB 290157 blocked this alteration ^[3]. SB 290157(0.1-10µM) inhibited C3aR internalization induced by 10 nM C3a in a concentration-dependent manner. In the presence of >1 µM concentrations of SB 290157 the internalization of the C3aR induced by C3a was reduced by ∼50% ^[4].

SB 290157 (trifluoroacetate salt) (1 mg/kg) treatment reduced microglial activation and cognitive deficits in lipopolysaccharide (LPS) induced mice. SB 290157 (trifluoroacetate salt) attenuated LPS-induced hippocampal neuroinflammation and inhibitory synapse related protein loss, contributing to improved cognitive function of mice ^[5]. SB 290157 (trifluoroacetate salt) was involved in the suppression of anti-OVA pAb-induced arthritis, injection of SB 290157 at concentrations of 30 mg/kg, SB 290157 was able to reduce joint swelling at 3 h, and inhibit about 50% inhibition of joint swelling ^[6].

References:
[1]. Ames R S, Lee D, Foley J J, et al. Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a receptor that demonstrates antiinflammatory activity in animal models[J]. The Journal of Immunology, 2001, 166(10): 6341-6348.
[2]. Han Y, Fukuda N, Ueno T, et al. Role of complement 3a in the synthetic phenotype and angiotensin II-production in vascular smooth muscle cells from spontaneously hypertensive rats[J]. American journal of hypertension, 2012, 25(3): 284-289.
[3]. Zheng J M, Wang S S, Tian X, et al. Sustained activation of C3aR in a human podocyte line impairs the morphological maturation of the cells[J]. Molecular medicine reports, 2020, 22(6): 5326-5338.
[4]. Ames R S, Lee D, Foley J J, et al. Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a receptor that demonstrates antiinflammatory activity in animal models[J]. The Journal of Immunology, 2001, 166(10): 6341-6348.
[5]. Li S, Li B, Zhang L, et al. A complement-microglial axis driving inhibitory synapse related protein loss might contribute to systemic inflammation-induced cognitive impairment[J]. International Immunopharmacology, 2020, 87: 106814.
[6]. Hutamekalin P, Takeda K, Tani M, et al. Effect of the C3a-receptor antagonist SB 290157 on anti-OVA polyclonal antibody-induced arthritis[J]. Journal of pharmacological sciences, 2010, 112(1): 56-63.