Glucocorticoid receptor agonist

Animal experiment:

Animal administration [1]Female Balb/c mice weighing approximately 20 g were used. Mice were administered the test compound and in Cremophor (po) approximately 60 min prior to LPS/D-gal administration. The volume of oral gavage was 0.15 mL. Then mice were administered LPS (E. coli LPS 055:85, 1.0 μg/mouse) plus D-gal (50 mg/kg) intravenously in 0.2 mL of pyrogen-free saline. One hour after LPS/D-gal, each mouse was anesthetized, bled by cardiac puncture, and collected for serum TNF-R and compound levels. Blood samples were centrifuged at 2500 rpm for 10-15 min, the serum was decanted, and samples were stored frozen at -70°C until transfer either for TNF-R determination or to Drug Metabolism and Pharmacokinetics for plasma concentration analysis by HPLC. The concentration of TNF-R in the serum was measured by a commercially available ELISA kit. ELISA was performed. All samples are assayed in duplicate.

References:

[1]. Riether, Doris et al.Nonsteroidal dissociated glucocorticoid agonists containing azaindoles as steroid A-ring mimetics. Journal of Medicinal Chemistry (2010), 53(18), 6681-6698.