tak-875 and Obesity

The free fatty acid receptor 4 (FFA4) has emerged as a promising anti-diabetic target due to its function in improvement of insulin secretion and insulin resistance. The FFA4 agonist TUG-891 revealed great potential as a widely used pharmacological tool, but it has been suffered from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β-oxidation. To identify metabolically stable analog without influence on physiological mechanism of TUG-891, we tried to incorporate deuterium at the α-position of phenylpropionic acid to afford compound 4 (GPU-028). As expected, GPU-028 revealed a longer half-life (T

Topics: Animals; Biphenyl Compounds; CHO Cells; Cricetulus; Deuterium; Diet, High-Fat; Dose-Response Relationship, Drug; Drug Discovery; Humans; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Obesity; Phenylpropionates; Propionates; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Structure-Activity Relationship