What question did this study set out to answer?

To identify and characterize a potent, selective non-peptide antagonist targeting the CXCR2 chemokine receptor to investigate its role in neutrophil activation and chemotaxis.

April 1, 1998Journal of Biological ChemistryOpen Access

Identification of a Potent, Selective Non-peptide CXCR2 Antagonist That Inhibits Interleukin-8-induced Neutrophil Migration

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Authors

JWJohn R. WhiteFranciscan University of Steubenville JLJudithann M. LeeGlaxoSmithKline (United States)PYPeter R. YoungGoddard Space Flight Center

Discussion

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Implication

Preclinical investigation reveals that selective CXCR2 antagonist SB 225002 blocks IL-8-driven neutrophil migration in rabbit models, indicating a therapeutic pathway for inflammatory diseases.

Key Points

To identify and characterize a potent, selective non-peptide antagonist targeting the CXCR2 chemokine receptor to investigate its role in neutrophil activation and chemotaxis.
Discovered and chemically optimized the small-molecule antagonist SB 225002 using high-throughput screening.
Measured binding affinity and selectivity against CXCR1 and four other seven-transmembrane G-protein coupled receptors using radioligand displacement assays.
Evaluated functional inhibition of IL-8- and GROalpha-induced neutrophil chemotaxis in vitro (human and rabbit) and neutrophil margination in vivo in rabbits.
SB 225002 inhibited 125I-IL-8 binding to CXCR2 with an IC50 of 22 nM, demonstrating >150-fold selectivity over CXCR1 and other tested receptors.
In vitro assays showed potent inhibition of human and rabbit neutrophil chemotaxis induced by both IL-8 and GROalpha.
In vivo administration selectively blocked IL-8-induced neutrophil margination in rabbits.

Cite This Study

White et al. (1998) studied this question.

synapsesocial.com/papers/6a021b984e84148937d8b963 https://doi.org/10.1074/jbc.273.17.10095

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April 1, 1998Journal of Biological ChemistryOpen Access

Identification of a Potent, Selective Non-peptide CXCR2 Antagonist That Inhibits Interleukin-8-induced Neutrophil Migration

View Full Paper

Ask AI

Bookmark

Authors

JWJohn R. WhiteFranciscan University of Steubenville JLJudithann M. LeeGlaxoSmithKline (United States)PYPeter R. YoungGoddard Space Flight Center

Discussion

Member takes

Implication

Preclinical investigation reveals that selective CXCR2 antagonist SB 225002 blocks IL-8-driven neutrophil migration in rabbit models, indicating a therapeutic pathway for inflammatory diseases.

Key Points

To identify and characterize a potent, selective non-peptide antagonist targeting the CXCR2 chemokine receptor to investigate its role in neutrophil activation and chemotaxis.
Discovered and chemically optimized the small-molecule antagonist SB 225002 using high-throughput screening.
Measured binding affinity and selectivity against CXCR1 and four other seven-transmembrane G-protein coupled receptors using radioligand displacement assays.
Evaluated functional inhibition of IL-8- and GROalpha-induced neutrophil chemotaxis in vitro (human and rabbit) and neutrophil margination in vivo in rabbits.
SB 225002 inhibited 125I-IL-8 binding to CXCR2 with an IC50 of 22 nM, demonstrating >150-fold selectivity over CXCR1 and other tested receptors.
In vitro assays showed potent inhibition of human and rabbit neutrophil chemotaxis induced by both IL-8 and GROalpha.
In vivo administration selectively blocked IL-8-induced neutrophil margination in rabbits.

Cite This Study

White et al. (1998) studied this question.

synapsesocial.com/papers/6a021b984e84148937d8b963 https://doi.org/10.1074/jbc.273.17.10095

Also Consider

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