SB225002

SB225002, a potent, selective and non-peptide CXCR2 antagonist, inhibits ¹²⁵I-IL-8 binding to CXCR2 with an IC₅₀ of 22 nM. IC50 & Target: IC50: 22 nM (CXCR2)^[1] In Vitro: SB225002 (SB 225002) is an antagonist of ¹²⁵I-IL-8 binding to CXCR2 with an IC₅₀=22 nM. SB225002 shows >150-fold selectivity over CXCR1 and four other 7-TMRs tested. SB225002 is a potent antagonist of rabbit CXCR2, inhibiting rabbit PMN chemotaxis in response to optimal concentrations of human IL-8 or GROα (IC₅₀ values of 30 and 70 nM, respectively. In these cells (PMN, HL60, CXCR1-RBL-2H3), SB225002 produces a concentration-dependent inhibition of both IL-8- and GROα-mediated calcium mobilization with IC₅₀ values of 8 and 10 nM, respectively. In 3ASubE cells stably transfected with CXCR2, SB 225002 dose-dependently inhibits calcium mobilization induced by both GROα and IL-8, with IC₅₀ values of 20 and 40 nM, respectively^[1]. WHCO1 cells treated with SB225002 exhibits a 40% reduction in cell proliferation. Blocking CXCR2 signaling in WHCO1 cells with 400 nM SB225002 (SB 225002) significantly decreases cell proliferation by ~40% to 50%^[2]. In Vivo: SB225002 (SB 225002) selectively blocks IL-8-induced neutrophil margination in rabbits^[1]. CXCR2 is blocked using the selective antagonist SB225002 (2 mg/kg) or neutralizing CXCR2 antiserum. The CXCR2 antagonist SB225002 decreases neutrophil counts in ischemic hemispheres of ApoE^−/− mice on Western diet and wildtype mice on normal diet^[3]. SB225002 significantly attenuates microglial activation and BBB damage, increases myelination, and reduces astrogliosis in the white matter after LPS-sensitized HI^[4].