Product Overview
Reparixin L-lysine salt is an inhibitor of interleukin 8 receptor alpha (CXCR1) and beta (CXCR2) with IC50 value of 5.6 nM and 80 nM respectively. CXCR1 and 2 belong to class A of 7-transmembrane G protein coupled receptor, and they share 78% amino acid identity. They are specific receptors for interleukin-8 which is a chemokine. They are mainly expressed in the neutrophils, where they mediate neutrophil migration to the site of inflammation. In addition, they are also involved in tumor aggressive growth and metastasis of human malignant melanoma. Structural and biochemical study identified that Reparixin L-lysine salt had non-competitive allosteric interaction with CXCR1 and 2, by which blocking CXCR1 and CXR2 in an inactive conformation, and thus suppressed receptor-induced intracellular signaling cascade and cellular response. When CXCR1 were expressed in L1.2 cells, cell migration induced by 10 nM CXC8 was significantly inhibited by reparixin L-lysine salt. In mouse model, treatment of reparixin L-lysine salt after introduction of injury significantly (15 mg/ kg/ day for 7 days) suppressed secondary degeneration by reducing CXC8-dependent oligodendrocyte apoptosis, migration to the injury site of neutrophils and ED-1-positive cells. Additionally, the level of macrophage-inflammatory protein-2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1 beta was also reduced, and the proliferation of glial fibrillary acidic protein-positive cells was significantly reduced. In mouse ischemia model, pre-treatment with reparixin reduced the motor deficits, myeloperoxidase activity and IL-1b level. Furthermore, ischemic injury was also attenuated.
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