All three share the His-Phe-Arg-Trp core that melanocortin receptors recognise. Melanotan I (afamelanotide) is a linear 13-residue analogue. Melanotan II and PT-141 (bremelanotide) are cyclic heptapeptides closed by a lactam bridge between aspartic acid and lysine, and they differ only at the C-terminus: an amide in Melanotan II and a free acid in PT-141.

In the laboratory they are used as reference agonists for the different melanocortin receptor subtypes. Medicinal chemistry papers use Melanotan II as a template for finding functionally selective agonists.