Key takeaways
- ✓Five receptors, MC1R to MC5R, with distinct tissue roles.
- ✓Melanotan II is non-selective; afamelanotide leans toward MC1R; setmelanotide targets MC4R.
- ✓Selectivity explains why related peptides have such different profiles.
The five receptors
All five are G-protein-coupled receptors that bind peptides derived from the precursor POMC.
- MC1R: mainly pigmentation in skin and hair follicles.
- MC2R: the ACTH receptor in the adrenal cortex.
- MC3R and MC4R: central regulation of energy balance and appetite, with MC4R also involved in sexual function.
- MC5R: exocrine glands.
Non-selective versus selective ligands
Melanotan II is a cyclic heptapeptide that activates several melanocortin receptors. Afamelanotide, a linear analogue of alpha-MSH, is more MC1R-directed and is approved in some regions for a rare photosensitivity disorder. PT-141 (bremelanotide), a metabolite-related analogue, has stronger activity at MC4R, and setmelanotide is a selective MC4R agonist approved for specific genetic obesity conditions.
Why this matters for comparisons
When two melanocortin peptides are compared, the right question is rarely which is stronger, but which receptors each engages. Our comparison pages for these pairs are organised around that point.
Compounds mentioned
PT-141
Cyclic melanocortin-receptor agonist
Melanotan II
Non-selective cyclic melanocortin agonist
Afamelanotide
Potent α-MSH analogue acting mainly at MC1R
Setmelanotide
Selective MC4R agonist
More guides
Cite this page
peptide.wiki. (2026). The melanocortin system explained: MC1R to MC5R. peptide.wiki. https://www.peptide.wiki/guides/melanocortin-system-explained