Reparixin

Reparixin is a non-competitive allosteric inhibitor of the chemokine receptors CXCR1 and CXCR2 activation with IC₅₀s of 1 and 100 nM, respectively. 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: Reparixin is an inhibitor of CXCL8 receptor CXCR1 and CXCR2 activation, has been shown to attenuate inflammatory responses in various injury models. Spontaneously hypertensive rats (SHR) are administered a subcutaneous injection of Reparixin (5 mg/kg) daily for 3 weeks. Reparixin effectively decreases systolic blood pressure and increased the blood flow^[3]. Reparixin reduces the levels of IL-1β in the brain after middle cerebral artery occlusion/reperfusion (MCAo) in mice. Bars represent levels of IL-1β (pg/100 mg) measured by ELISA in the brain tissues of mice subjected or not (SHAM) to MCAo and pretreated with vehicle or Reparixin (30 mg/kg, s.c.)^[4].