FAA1 agonist-1

Cell experiment:

Human hepatocyte HepG2 cells are cultured at 37°C, 5% CO2 in DMEM supplemented with 10% fetal bovine serum, 50 μg/mL streptomycin and 50 IU/mL penicillin. Cells are seeded in a 96-well plate (2×104 cells/well) and cultured with GPR40 agonist 4 (compound 20) in DMEM for 24 h. FGPR40 agonist 4 is measured in three independent experiments[1].

Animal experiment:

8 weeks old normal male SD rats after 1 week adaptation are fasted overnight (12 h), weighted, bled via the tail vein, and randomized into 5 groups (n=6 for each group). Rats are administrated orally with a single doses of vehicle (0.5% methylcellulose aqueous solution) or GPR40 agonist 4 (compound 20) (1, 3 and 10 mg/kg suspended in vehicle) and subsequently dosed orally with glucose aqueous solution (3 g/kg) after 60 min. Blood samples are collected immediately before drug administration (~60 min), before glucose challenge (0 min), and at 15, 30, 60 and 120 min post-dose. The blood glucose is measured by blood glucose test strips[1].

References:

[1]. Li Z, et al. Discovery of phenylsulfonyl acetic acid derivatives with improved efficacy and safety as potent free fatty acid receptor 1 agonists for the treatment of type 2 diabetes. Eur J Med Chem. 2017 Sep 29;138:458-479.