Article Figures & Data
Figures
- Fig. 1.
Antagonism by danirixin and navirixin of CXCL8 at the CXCR2 receptor as assessed by Ca2+-flux studies in hCXCR2-expressing CHO cells. (A) Danirixin (B form) was preincubated for 30 minutes and shows competitive antagonism. Results are expressed as mean ± S.E.M.; n = 3. (B) Apparent uncompetitive antagonism by navirixin at the CXCR2 receptor under the identical experimental conditions as (A).
- Fig. 2.
Reversibility of danirixin and navirixin binding to hCXCR2-expressing CHO cells, as assessed by Ca2+-flux studies. (A) Danirixin (B form) binds reversibly to CXCR2. Compound was preincubated for 90 minutes, followed by a 180-minute washout before determining cellular response to CXCL8. Results are expressed as mean ± S.E.M.; n = 3. (B) Navirixin also binds reversibly to CXCR2 under the identical experimental conditions as in (A).
- Fig. 3.
CD11b expression levels on neutrophils measured by flow cytometry in rat whole blood following ex vivo challenge with CXCL2 of blood collected 1 hour after oral dosing of danirixin (B form) at 0.3, 3, and 30 mg/kg to groups of 3–5 rats. The EC50 of CXCL2 trended to increase with increasing dose of compound.
- Fig. 4.
Effect of danirixin (A form) on CXCL1-mediated CD11b upregulation on neutrophils in human whole blood. Data are expressed as mean (S.E.M.) using three donors.
- Fig. 5.
Inhibition by orally administered danirixin (B form) of LPS-induced neutrophilia in bronchoalveolar lavage of (A) fasted rats or (B) fed rats Left: means and S.E.M. of groups of five rats each; right: means with individual values per rat. **P < 0.01. For (B), the indicated point in on the right was removed from the analysis in the left.
- Fig. 6.
Effect of repeat dosing of orally administered danirixin (B form) on inhibition of LPS-induced neutrophilia in bronchoalveolar lavage in rat. Left: means and S.E.M. of groups of five rats each; right: means with individual values per rat.
- Fig. 7.
Inhibition by orally administered danirixin (B form) of ozone-induced neutrophilia in the rat. Left: means and S.E.M. from groups of five rats; right: means with individual values. **P < 0.01
- Fig. 8.
Dose-related effects of danirixin on ex vivo shift in CXCL2-induced CD11b upregulation and inhibition of LPS-induced neutrophilia in the rat.
