TGR5 is a transmembrane G protein-coupled receptor that is activated by bile acid. INT-777 is a semisynthetic bile acid that acts as an agonist of TGR5 (EC50 = 0.82 μM). It is active in vivo, stimulating the secretion of glucagon-like peptide-1 (GLP-1) in mice when given orally (30 mg/kg) after a glucose challenge, particularly when given with a dipeptidyl-peptidase-4 inhibitor. INT-777 increases energy expenditure and reduces hepatic steatosis and adiposity in mice subjected to diet-induced obesity. It also stimulates insulin secretion in pancreatic β cells, reduces inflammation and inhibits atherosclerosis in mice, and promotes chloride secretion through cystic fibrosis transmembrane conductance regulator (CFTR) in Calu-3 airway epithelial cells.
