Reparixin L-lysine salt (Repertaxin L-lysine salt) is an allosteric chemokine receptor 1/2 (CXCR1/2) activation inhibitor.

CXCR2:100 nM (in cells), CXCR1:1 nM (in cells), CXCR1:5.6 nM (CXCR1wt, in L1.2 cells), CXCR1:80 nM (CXCR1Ile43Val; in L1.2 cells)

Reparixin is a potent CXCL8-induced inhibitor 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.Reparixin is a non-competitive allosteric inhibitor of IL-8 receptors with a 400-fold higher efficacy in inhibiting CXCR1 activity than CXCR2[2]. 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].

The pharmacokinetics and metabolism of Reparixin were investigated in rats and dogs following the intravenous administration of [14C]-Reparixin L-lysine salt. Plasma protein binding of Reparixin is >99% in both laboratory animals and humans up to 50 μg/mL, but decreases at higher concentrations. Radioactivity rapidly distributes into rat tissues, yet the volume of distribution at steady state (Vss) is low (approximately 0.15 L/kg) in both rats and dogs. Reparixin is eliminated more rapidly in rats (t1/2~0.5 h) than in dogs (t1/2~10 h)[3].