Structural insights into neuropeptide receptor could aid obesity drug discovery

Neuropeptide Y is a major brain neurotransmitter and the most powerful known stimulant of food intake, an effect primarily mediated through activation of the Y1 receptor. Compounds that block the receptor, known as Y1 receptor antagonists, have shown clinical potential in the treatment of obesity as well as cancer and bone loss. But their clinical usage has been hampered by low potency and selectivity, poor brain penetration ability or lack of oral bioavailability. To address these issues, researchers recently solved the crystal structures of the human Y1 receptor bound to two structurally diverse selective antagonists. According to the authors, these insights can aid efforts to discover drugs that target neuropeptide Y receptors for the treatment of obesity and other conditions. The study, published in Nature, was partly funded by NHLBI.