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Ipamorelin emerged from this programme as the first truly selective GHS-R1a agonist , a pentapeptide incorporating alpha-aminoisobutyric acid (Aib) at position 1, His at position 2, the unnatural D-2-naphthylalanine residue at position 3, D-Phe at position 4, and C-terminal Lys-NH2 and a structural solution that achieves high-affinity GHS-R1a binding and potent GH release while eliminating the receptor interactions responsible for prolactin and cortisol co-stimulation in non-selective first-generation GH secretagogues