* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. For research purposes only.
Melanotan 1 (MT-1) and Melanotan 2 (MT-2) are both synthetic analogs of alpha-melanocyte-stimulating hormone (alpha-MSH), the endogenous 13-residue peptide that activates melanocortin receptors, but they are structurally different molecules with different receptor profiles. Melanotan 1, also known as afamelanotide, is a linear 13-residue peptide with the sequence Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂, the molecular formula C₇₈H₁₁₁N₂₁O₁₉, a molecular weight of 1646.8 g/mol, and CAS number 75921-69-6. Melanotan 2 is a cyclic heptapeptide with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂, the molecular formula C₅₀H₆₉N₁₅O₉, a molecular weight of 1024.2 g/mol, and CAS number 121062-08-6. Both were developed at the University of Arizona in the 1980s as part of a program to produce alpha-MSH analogs with improved stability and potency. Both are supplied by Evo Amino as lyophilized research compounds.
Comparison table
Property
Melanotan 1 (afamelanotide)
Melanotan 2
Structure
Linear 13-residue peptide
Cyclic heptapeptide, lactam bridge (Asp to Lys side chains)
Nle4, D-Phe7, cyclization, truncation to residues 4-10
Receptor profile (published binding studies)
MC1R-focused
Broader: MC1R, MC3R, MC4R, MC5R
Regulatory status
Approved implant product in some jurisdictions (Scenesse)
No approved product
Molecular facts are from the Evo Amino catalog entries for each compound.
What modifications does Melanotan 1 carry relative to alpha-MSH?
Melanotan 1 differs from native alpha-MSH at two positions: norleucine replaces methionine at position 4, and D-phenylalanine replaces L-phenylalanine at position 7. The full name in the literature is [Nle4, D-Phe7]-alpha-MSH, abbreviated NDP-alpha-MSH or NDP-MSH. The norleucine substitution removes the oxidizable methionine sulfur, which is a stability improvement, since methionine oxidation to the sulfoxide inactivates the native peptide. The D-phenylalanine at position 7 sits in the His-Phe-Arg-Trp core that all melanocortin receptors recognize, and its inverted stereochemistry both resists proteolysis and, per receptor binding studies, increases affinity and prolongs activity at the receptor. The rest of the sequence is native alpha-MSH, including the N-terminal acetyl and C-terminal amide.
What is the cyclic structure of Melanotan 2?
Melanotan 2 is built from the same His-D-Phe-Arg-Trp core but truncated to the alpha-MSH 4-10 region and cyclized through a lactam bridge between the side chains of an aspartate (replacing glutamate 5) and a lysine (replacing glycine 10). The N-terminal norleucine is retained as an acetylated residue outside the ring. Cyclization locks the core into a conformation that mimics the receptor-bound turn structure of the linear peptide, which the developing group reported produced a compound with higher potency and longer activity than the linear analog at 40% of its size. The lactam is a side-chain-to-side-chain amide bond, chemically stable, and not a disulfide, so it does not carry the oxidative sensitivity of cysteine-bridged cyclic peptides.
How does receptor selectivity differ between the two?
Published receptor binding and functional studies characterize Melanotan 1 as relatively selective for the melanocortin 1 receptor (MC1R), the receptor expressed on melanocytes, with lower activity at MC3R, MC4R, and MC5R. Melanotan 2, by contrast, is reported as a potent agonist across MC1R, MC3R, MC4R, and MC5R, with particular activity at MC4R that the linear analog lacks. This broader profile is attributed to the cyclic constraint: the locked conformation fits the binding pockets of multiple receptor subtypes, whereas the flexible linear peptide is more dependent on the full-length sequence context that favors MC1R. Neither compound has meaningful activity at MC2R, the ACTH receptor, which requires a sequence motif both lack.
The difference matters for research design. Work on melanocyte biology and MC1R signaling uses Melanotan 1 to minimize off-target receptor engagement. Work on MC4R, which is expressed in the central nervous system and studied in the context of energy homeostasis and other hypothalamic pathways, uses Melanotan 2 or its MC4R-focused derivatives such as bremelanotide (PT-141), which is the des-acetyl, free-acid metabolite of Melanotan 2.
What does published research measure for each compound?
For Melanotan 1, the research literature centers on MC1R activation in melanocyte and keratinocyte models, measured through cyclic AMP accumulation, tyrosinase expression and activity, and eumelanin synthesis markers, together with the controlled clinical program that led to the approved afamelanotide implant. That program studied the compound in a genetic photodermatosis and reported on melanin density, photoprotection endpoints, and safety over multi-year follow-up. For Melanotan 2, the literature is broader and less controlled: receptor pharmacology across the melanocortin subtypes, MC4R-mediated effects in rodent hypothalamic models, and early human studies from the 1990s that characterized its activity and also identified effects attributable to MC3R and MC4R engagement that Melanotan 1 does not produce. Melanotan 2 has no approved pharmaceutical form, and much of the recent literature on it concerns analysis of unregulated products rather than controlled study.
What is the regulatory status of each?
Afamelanotide, the pharmaceutical name for Melanotan 1, is an approved prescription product in the European Union, Australia, and the United States under the brand name Scenesse, formulated as a subcutaneous implant for a specific indication. That approval applies to the pharmaceutical product and its manufacturer; research-grade Melanotan 1 sold as a lyophilized peptide is a separate material with no regulatory approval for any use. Melanotan 2 has never been approved as a pharmaceutical in any jurisdiction, and regulators in several countries have issued warnings about unregulated Melanotan 2 products. Both compounds in Evo Amino's catalog are supplied strictly for laboratory research.
What are the analytical considerations?
Melanotan 1 at 13 residues and 1647 Da gives a straightforward reverse-phase HPLC profile with predominantly +2 and +3 ions on electrospray mass spectrometry; the tryptophan and tyrosine give it strong absorbance at 280 nm, and the D-phenylalanine makes chiral purity a relevant check, since the L-epimer nearly co-elutes. Melanotan 2 at 1024 Da presents as a compact single peak; the analytical question specific to it is confirming the lactam cyclization, since the uncyclized linear precursor has a mass 18 Da higher (one water molecule not eliminated) and can be resolved by mass spectrometry. Both contain tryptophan and are stored protected from light. A Certificate of Analysis reporting observed versus theoretical mass alongside HPLC purity confirms identity for either.
How should researchers choose between them?
The receptor question decides it. MC1R-focused work uses Melanotan 1. Multi-receptor or MC4R-focused work uses Melanotan 2. The two are not interchangeable: they differ in size, in conformation, in receptor profile, and in the body of published evidence behind each. The Melanotan 2 melanocortin receptor overview on a sister brand covers MT-2's receptor pharmacology in more depth.
All compounds referenced in this article are supplied for research purposes only and are not for human use. Nothing here describes or endorses any use of these materials outside laboratory research. These products are not intended to diagnose, treat, cure, or prevent any disease.
Stay in the loop
New compounds, research updates & exclusive subscriber deals.
