CX4338 is a CXCL8-mediated chemokine inhibitor with the activity of inhibiting CXCR2-mediated cell migration. CX4338 selectively inhibits CXCR2-mediated β-arrestin-2 recruitment and receptor internalization while enhancing CXCR2-mediated MAPK activation. CX4338 also inhibited CXCL8-induced chemotaxis, showing efficacy in CXCR2-overexpressing cells and human neutrophils. In vivo, CX4338 significantly reduced LPS-induced neutrophil numbers in mouse bronchoalveolar lavage fluid. The mechanism of action of CX4338 is to selectively inhibit CXCR2-mediated β-arrestin-2 activation, which is sufficient to inhibit CXCL8-mediated chemotaxis.
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