Reparixin (L-lysine salt)

Reparixin L-lysine salt is a potent and specific allosteric inhibitor of both CXCL8 receptors CXCR1/2, it inhibits weakly CXCR2-mediated cell migration (IC₅₀=100 nM), whereas it strongly blocks CXCR1-mediated chemotaxis (IC₅₀=1 nM). IC50 & Target: IC50: 5.6/80 nM (CXCR1^wt/CXCR1^Ile43Val, in L1.2 cell)^[1] In Vitro: Reparixin is a potent functional inhibitor of CXCL8-induced biological activities on human PMNs with a marked selectivity (around 400-fold) for CXCR1, as shown in specific experiments on CXCR1/L1.2 and CXCR2/L1.2 transfected cells and on human PMNs. The efficacy of Reparixin is significantly lower in L1.2 cells expressing Ile43Val CXCR1 mutant (IC₅₀ values of 5.6 nM and 80 nM for CXCR1 wt and CXCR1 Ile43Val, respectively)^[1]. Reparixin is a non-competitive allosteric inhibitor of IL-8 receptors with a 400-fold higher efficacy in inhibiting CXCR1 activity than CXCR2^[2]. In Vivo: The pharmacokinetics and metabolism of Reparixin are investigated in rats and dogs after intravenous administration of [¹⁴C]-Reparixin L-lysine salt. Plasma protein binding of Reparixin is >99% in the laboratory animals and humans up to 50 µg/mL, but lower at higher concentrations. Although radioactivity is rapidly distributed into rat tissues, V_ss is low (about 0.15 L/kg) in both rat and dog. Nevertheless, Reparixin is more rapidly eliminated in rats (t_1/2~0.5 h) than in dogs (t_1/2~10 h)^[3].