Figure 3.

Compound 4b binding with the enzymes and its in vitro and in vivo activities. (A) Binding with human mPGES-1; (B) binding with mouse mPGES-1; (C) dose-dependent inhibition of human mPGES-1 (n = 3); (D) dose-dependent inhibition of mouse mPGES-1 (n = 3); (E) and (F) data from in vivo assays using the mouse air-pouch model (n = 5 for each group) with 4b or celecoxib given SC or PO. Normalized levels of PGE₂ in kidney collected following the formation of air-pouches on the backs of mice and injection of the pro-inflammatory agent carrageenan to stimulate PGE2 synthesis. Mice were treated SC or PO with vehicle, 4b, or celecoxib at various dose conditions for 24 hours prior to collection of the kidney samples (analyzed for PGE₂ by ELISA). Statistical results from the one-way ANOVA analysis of the data in panel E with post hoc tests: p = 0.0035 for 0.1 mg/kg 4b (SC) vs Vehicle; p < 0.0001 for 1 mg/kg 4b (SC) vs Vehicle, 10 mg/kg 4b (SC) vs Vehicle, and 10 mg/kg Celecoxib (SC) vs Vehicle; p = 0.0012 for 1 mg/kg 4b (SC) vs 0.1 mg/kg 4b (SC); p = 0.0002 for 10 mg/kg 4b (SC) vs 0.1 mg/kg 4b (SC); p = 0.0003 for 10 mg/kg Celecoxib (SC) vs 0.1 mg/kg 4b (SC); p = 0.3176 for 10 mg/kg 4b (SC) vs 1 mg/kg 4b (SC); and p = 0.6424 for 10 mg/kg Celecoxib (SC) vs 10 mg/kg 4b (SC). Statistical results from the one-way ANOVA analysis of the data in panel F with post hoc tests: p = 0.0281 for 5 mg/kg 4b (PO) vs Vehicle; p = 0.0011 for 10 mg/kg 4b (PO) vs Vehicle; p = 0.0008 for 50 mg/kg Celecoxib (PO) vs Vehicle; p = 0.0481 for 10 mg/kg 4b (PO) vs 5 mg/kg 4b (PO); p = 0.0221 for 50 mg/kg Celecoxib (PO) vs 5 mg/kg 4b (PO); and p = 0.4986 for 50 mg/kg Celecoxib (PO) vs 10 mg/kg 4b (PO).