RS 504393

RS 504393 is a selective CCR2 chemokine receptor antagonist (IC₅₀ values are 89 nM and > 100 μM for inhibition of human recombinant CCR2 and CCR1 receptors respectively). IC50 & Target:IC50: 89 nM (CCR2)^[5] In Vitro:RS 504393 inhibits the MCP-1-induced chemotaxis with an IC₅₀ of 330 nM. RS 504393 treatment suppresses allergen induced β-hexosaminidase release significantly. Without allergen priming, MCP-1 induces mast cell degranulation, which is completely suppressed by RS 504393^[4]. In Vivo:RS504393 (0.3-3 μg) with CCL2 progressively blocks thermal hyperalgesia dose-dependently in mice^[1]. RS 504393 (5 mg/kg, i.v.) supresses the elevated numbers of leukocytes and increased total protein content in BALF induced by The LPS. RS504393 significantly down regulates the LPS-induced elevation of IL-1β, PAI-1 mRNA and protein expressions. RS504393 significantly suppresses induced lung edema, protein-rich fluid, polymorphonuclear accumulation and bronchial wall thickening induced by LPS^[2]. RS-504393 significantly reduces renal pathology, especially the extensive interstitial fibrosis mediated by decrease in type I collagen synthesis in a UUO model^[3].