Inhibitor of CXCL8 receptor and CXCR1/CXCR2 activation
CAS：266359-83-5
分子式：C14H21NO3S
分子量：283.39
纯度：98%
存储：Store at -20°C

Background:

Reparixin is a non-competitive allosteric inhibitor of CXCR1/2.

CXCR is a 7-transmembrane G protein-coupled receptor. CXCR plays a critical role in the development of different models of ALI Following engagement of this receptor, the Gbg-complex dissociates from the Gai-subunit and can activate phosphoinositide-3 kinase, different subtypes of phospholipase C and P-Rex-1. The downstream effectors of these molecules initiate a broad range of functional responses, including arrest from rolling, cytoskeletal rearrangement, cell polarization, chemotaxis, degranulation and respiratory burst.

Reperixin, specifically blocks CXCR1/2-mediated mouse and human neutrophil migration in vitro without affecting other receptors. Reparixin reduces ligand binding to human CXCR1 and CXCR2, calcium influx and downstream signalling in response to human CXCL8 and neutrophil recruitment into the liver in a mouse model of ischaemia-reperfusion injury. Reparixin reduced neutrophil recruitment and liver damage by approximately 30% and 80% in a model of ischaemiareperfusion injury.[1,2]

Reparixin reduced oligodendrocyte apoptosis, migration to the injury site of neutrophils and ED-1-positive cells. The best beneficial outcome of reparixin treatment will require 7-day administration either by i.p. route (15 mg/kg) or subcutaneous infusion via osmotic pumps (10 mg/kg), reaching a steady blood level of 8 μg/ml. Methylprednisolone are used as a reference drug, and such treatment reduced cytokine production but failed to affect the rate of hind limb recovery. [1,2]

参考文献:
[1] A Zarbock, M Allegretti and K Ley.  Therapeutic inhibition of CXCR2 by Reparixin attenuates acute lung injury in mice. British Journal of Pharmacology (2008) 155, 357–364.
[2] Alfredo Gorio, Laura Madaschi, Giorgia Zadra et al.  Reparixin, an Inhibitor of CXCR2 Function, Attenuates Inflammatory Responses and Promotes Recovery of Function after Traumatic Lesion to the Spinal Cord. doi:10.1124/jpet.107.123679.