Allosteric inhibition of CXCR1/2 by an orally bioavailable chemokine receptor inhibitor attenuates allergic lung inflammation in mice

Abstract

CXCR1/2 chemokine receptors are expressed on the surface of inflammatory cells. We previously reported that parenterally-administered reparixin, a noncompetitive allosteric inhibitor of CXCR1 and CXCR2, inhibits allergic airway inflammation. Ladarixin is a second generation orally bioavailable dual CXCR1/2 inhibitor that binds an allosteric pocket of the trans-membrane region of both receptors with a 100-fold higher affinity than first generation CXCR1/2 inhibitors. Here we investigated whether oral ladarixin also inhibits allergic airway inflammation.