Discovery of a β-MSH-derived MC-4R selective agonist

A series of novel, disulfide-constrained human β-melanocyte stimulating hormone (β-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food intake and body weight models.