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Overview
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Background
SB 265610 is a potent CXCR2 antagonist that inhibits CINC-1-mediated Ca2+ mobilization with IC50 value of 3.4nM [1] [2]. CXCR2 is an integral membrane protein that specifically binds and responds to cytokines of the CXC chemokine family.In isolated rat neutrophils stimulated with rat CINC-1, SB 265610 inhibited Ca2+ mobilization induced by CINC-1 with IC50 value of 3.4 nM in a dose-dependent way, while inhibited Ca2+ mobilization induced by C5a only with IC50 value of 6.8uM, which showed selectivity of the antagonist for CXCR2 [1]. In equilibrium saturation binding studies, SB265610 inhibited the binding of interleukin-8 without affecting the Kd. While, IL-8 couldn’t prevent binding of SB265610. SB265610 is an allosteric inverse agonist at the CXCR2 receptor [2].In a hyperoxia rat model, newborn rats increased lung neutrophil content. Treatment with SB-265610 reduced hyperoxia-induced neutrophil accumulation in bronchoalveolar lavage and whole lung myeloperoxidase accumulation [1].
[1]. Auten RL, Richardson RM, White JR, et al. Nonpeptide CXCR2 antagonist prevents neutrophil accumulation in hyperoxia-exposed newborn rats. J Pharmacol Exp Ther, 2001, 299(1): 90-95.
[2]. Bradley ME, Bond ME, Manini J, et al. SB265610 is an allosteric, inverse agonist at the human CXCR2 receptor. Br J Pharmacol, 2009, 158(1): 328-338.
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