Melanotan 1 and Melanotan 2 are not licensed medicines in the United Kingdom and are not approved for human or veterinary use. This article compares the two compounds at the structural and receptor level for scientific reference. It contains no usage or dosing information.
Overview
Melanotan 1 (MT-1, also known as afamelanotide) and Melanotan 2 (MT-2) are synthetic analogues of alpha-melanocyte-stimulating hormone (α-MSH), a naturally occurring neuropeptide. They are often discussed as if they were two strengths of the same thing. They are not: they differ in structure, in stability and, most importantly, in how many melanocortin receptors they activate. This article sets out those differences side by side.
Structural differences
| Feature | MT-1 (afamelanotide) | MT-2 |
|---|---|---|
| Structure | Linear peptide | Cyclic peptide |
| Length | 13 residues: α-MSH with norleucine at position 4 and D-phenylalanine at position 7 | Cyclic heptapeptide built on the α-MSH core sequence, closed by a lactam bridge |
| Receptor selectivity | Comparatively MC1R-selective | Non-selective: MC1R, MC3R, MC4R and MC5R |
| Resistance to peptidases | Improved over native α-MSH by the two substitutions | Higher still: the ring resists exopeptidase attack |
| UK regulatory status | Not licensed for general use | Not licensed |
Receptor selectivity
There are five melanocortin receptors, MC1R to MC5R, all G protein-coupled and distributed across very different tissues. MC1R is associated principally with pigmentation; MC3R and MC4R with energy balance and central signalling; MC5R with exocrine function.
Selectivity is therefore the property that matters most when comparing these two compounds. MT-1 is comparatively MC1R-selective, although selectivity is relative and narrows at high concentrations. MT-2 activates four of the five receptors, so a single application engages several systems at once.
For experimental design this cuts both ways. A study of MC1R signalling specifically is cleaner with MT-1. A study of melanocortin signalling broadly may use MT-2, but attributing any observed effect to one receptor then needs receptor-selective antagonists or knockout controls.
Where each appears in the literature
MT-1 has an unusually well-characterised pharmacokinetic and pharmacodynamic record for a compound in this class, which makes it useful as a reference melanocortin agonist. Structural work has also resolved how ligands are recognised at MC1R. See our MT-1 research summary.
MT-2 appears mostly in rodent models, where its breadth makes it a tool for studying MC4R signalling, energy balance, thermogenesis and peripheral nerve regeneration. Results in these models vary with diet, genetic background and housing conditions. See our MT-2 research summary.
Handling and stability
Both are supplied as lyophilised solids and stored at −20°C, protected from light and moisture. Reconstitution uses sterile bacteriostatic water added slowly down the vial wall, with gentle swirling rather than shaking. Our peptide reconstitution calculator works out the resulting concentration.
The cyclic structure makes MT-2 the more robust of the two in solution, but neither tolerates repeated freeze–thaw cycling well. Aliquoting a reconstituted stock into single-use volumes at the point of reconstitution protects the rest of the material.
Regulatory status in the United Kingdom
Both compounds fall under the oversight of the Medicines and Healthcare products Regulatory Agency (MHRA):
- Neither compound is licensed as a medicine for general use in the UK.
- The MHRA treats melanotan products sold for human use as unlicensed medicines, and selling them for that purpose is illegal under the Human Medicines Regulations 2012.
- An afamelanotide implant (Scenesse®) is authorised in the EU for one rare condition. That authorisation does not cover general use in the UK.
- Products sold for research purposes must not be represented as suitable for human use.
Summary
MT-1 and MT-2 are related melanocortin receptor agonists with different structures and, above all, different receptor profiles: MT-1 is comparatively MC1R-selective and linear; MT-2 is cyclic, more stable and acts across four receptors. Which one suits a study depends on whether the question is about one receptor or the melanocortin system as a whole.
For handling information, see our Peptide Reconstitution Guide and Peptide Storage Guide.