Ordering from the Americas?Switch to the US store
We don't ship to your country yet. We ship across Europe and the Americas. You can keep browsing.
Account
Research library, mechanism

Melanocortin receptors and their peptide ligands

The melanocortin system consists of five G-protein-coupled receptors, peptide agonists derived from proopiomelanocortin, and the endogenous antagonists agouti and agouti-related protein. Alpha-MSH, melanotan II, PT-141 and the fragment KPV all derive from or relate to this system.

Written by the Peptency editorial teamLast reviewed 7 studies checked in PubMed on 5 October 2026

Research-use information. This page summarises published literature and regulator records. It is not guidance for use, not medical advice, and not a statement that any material is suitable for use in people or animals.

What is the melanocortin system?

A 2006 review defines the system by its five G-protein-coupled receptors, its POMC-derived peptide agonists and its endogenous antagonists, and surveys its physiological roles.[4]

What does the receptor structure show?

Cryo-EM structures of full-length human MC4R bound to alpha-MSH, afamelanotide, bremelanotide and a small-molecule ligand show how different ligands engage the same receptor. A 2022 review covers melanocortin receptor ligands beyond the melanocyte-stimulating hormones and ACTH.[3],[1]

How do the catalog compounds relate to alpha-MSH?

Melanotan II is a lactam-bridged cyclic analogue of alpha-MSH(4-10) described as a potent and unselective agonist at human melanocortin receptors. PT-141 has the same cyclic core with a C-terminal acid in place of the amide. KPV is the C-terminal tripeptide of alpha-MSH, examined in cell and mouse inflammation studies.[2],[7],[6],[5]

Which compounds in the catalog belong to this group?

Cyclic heptapeptide melanocortin receptor agonistPT-141

C50H68N14O10, 1025.2 g/mol

Cyclic heptapeptide, alpha-MSH analogueMelanotan II

C50H69N15O9, 1024.2 g/mol

Tripeptide, C-terminal fragment of alpha-MSHKPV

C16H30N4O4, 342.43 g/mol

Research materials: PT-141, Melanotan II, KPV.

Which studies are cited on this page?

  1. [1] Yuan XC, Tao YX. Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin. Biomolecules. 2022;12.

    Review of melanocortin receptor ligands beyond melanocyte-stimulating hormones and ACTH.

    ReviewPMID 36291616DOI 10.3390/biom12101407

  2. [2] Tomassi S, Dimmito MP, Cai M, D'Aniello A, Del Bene A, Messere A, et al.. CLIPSing Melanotan-II to Discover Multiple Functionally Selective hMCR Agonists. J Med Chem. 2022;65:4007-4017.

    Replaced the lactam cyclisation of melanotan II with scaffold chemistry and profiled functional selectivity at human melanocortin receptors.

    ChemistryPMID 35188390DOI 10.1021/acs.jmedchem.1c01848

  3. [3] Zhang H, Chen LN, Yang D, Mao C, Shen Q, Feng W, et al.. Structural insights into ligand recognition and activation of the melanocortin-4 receptor. Cell Res. 2021;31:1163-1175.

    Cryo-EM structures of full-length human MC4R bound to alpha-MSH, afamelanotide, bremelanotide and a small-molecule ligand.

    Structural biologyPMID 34433901DOI 10.1038/s41422-021-00552-3

  4. [4] Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 2006;27:736-49.

    Review of melanocortin system physiology: receptors, POMC-derived agonists and endogenous antagonists.

    ReviewPMID 17077189DOI 10.1210/er.2006-0034

  5. [5] Luger TA, Scholzen TE, Brzoska T, Böhm M. New insights into the functions of alpha-MSH and related peptides in the immune system. Ann N Y Acad Sci. 2003;994:133-40.

    Review of alpha-MSH and related peptides in immunity and inflammation, including receptor expression on immune cells.

    ReviewPMID 12851308DOI 10.1111/j.1749-6632.2003.tb03172.x

  6. [6] Getting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. J Pharmacol Exp Ther. 2003;306:631-7.

    Compared KPV with other melanocortin peptides in a mouse model of crystal-induced peritonitis.

    Animal studyPMID 12750433DOI 10.1124/jpet.103.051623

  7. [7] Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, et al.. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58:1777-84.

    Pilot phase I study of melanotan-II in a small group of healthy volunteers (1996).

    Human studyPMID 8637402DOI 10.1016/0024-3205(96)00160-9

Data dates: citations read from PubMed 2026-10-05.