Melanotan II vs PT-141: structure, the one-atom difference, melanocortin receptor pharmacology, and handling
Melanotan II (MT-2) and PT-141 are cyclic heptapeptides from the same University of Arizona programme, and PT-141 is literally a metabolite of MT-2: the two differ by a single terminal group. Both are agonists at the melanocortin receptors, which is where almost all of their research interest lies. This guide compares their structures, explains what the melanocortin receptors are and why they matter to the research literature, and covers the handling points for two tryptophan-containing cyclic peptides. For laboratory research use only.
Side by side
| Melanotan II (MT-2) | PT-141 | |
| Sequence | Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 | Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH |
| C-terminus | Amide (–NH2) | Free acid (–OH) |
| Molecular weight | ≈ 1,024.2 g/mol | ≈ 1,025.2 g/mol |
| CAS number | 121062-08-6 | 189691-06-3 |
| Ring | Lactam bridge between Asp and Lys side chains (both) | Same |
| Receptor profile | Non-selective agonist: MC1R, MC3R, MC4R, MC5R | Non-selective agonist; most research attention on MC4R (and MC3R) |
| Origin | Hruby / Hadley group, University of Arizona, 1980s | Identified as the active metabolite of MT-2 in the 1990s |
| Oxidation / light-sensitive residue | Tryptophan (both) | Tryptophan |
| Solubility | Water, bacteriostatic water | Water, bacteriostatic water |
Where they come from
Both peptides descend from α-melanocyte-stimulating hormone (α-MSH), the 13-residue hormone that controls pigment production in skin and hair and has signalling roles in the brain. Native α-MSH is degraded in minutes. In the 1980s Victor Hruby, Mac Hadley and colleagues at the University of Arizona set out to make analogues that were more potent and more stable: substituting D-phenylalanine for L-phenylalanine at position 7 and norleucine for methionine at position 4 gave the linear analogue that is the ancestor of this family, and closing a lactam ring between the aspartate and lysine side chains gave a shorter, cyclic peptide that was more potent still. That cyclic heptapeptide is Melanotan II.
PT-141 is what MT-2 becomes when its C-terminal amide is hydrolysed to a carboxylic acid. It was identified as a metabolite of MT-2 and then developed in its own right because its receptor profile and physiological effects were not identical to the parent compound. The compound was later taken through pharmaceutical development as a regulated medicine for a specific indication; that programme’s data concern the approved product in its defined patient group and do not apply to a research reagent.
What the melanocortin receptors are
The five melanocortin receptors are G-protein-coupled receptors that signal through cAMP. MC1R on melanocytes controls eumelanin synthesis; MC2R is the ACTH receptor in the adrenal cortex (neither peptide activates it meaningfully); MC3R and MC4R are expressed in the brain, where MC4R in particular is a central regulator of energy balance and autonomic output; MC5R is found in exocrine glands and elsewhere. Because MT-2 and PT-141 activate four of the five, they are used in the literature as non-selective agonist tools, often alongside selective ligands and receptor-knockout animals to work out which receptor mediates a given response. A great deal of what is known about MC3R and MC4R biology was established using these and closely related peptides.
What the literature has studied
Receptor binding and signalling
The foundational work is in-vitro pharmacology: binding affinities and cAMP responses at each cloned human melanocortin receptor, structure–activity relationships of the cyclic scaffold, and the effect of the C-terminal group on potency and selectivity. This is the most accessible and reproducible use of either peptide in a laboratory.
Melanogenesis models
MT-2, as a potent MC1R agonist, has been used to study melanin synthesis in cultured melanocytes and in animal pigmentation models since the 1980s. Those models are where the “melanotan” name comes from.
Central melanocortin pathway studies
Both peptides have been used in rodent studies of the central MC3R/MC4R pathway, with PT-141 the more frequently used tool in that literature because of its receptor profile. These are mechanistic animal studies of a signalling pathway; they are not evidence of effects in people and should not be read as such.
Human data
MT-2 has no regulatory approval anywhere and no controlled clinical data as a research reagent; regulators in several countries have issued warnings about its unregulated sale for human use. PT-141 has a pharmaceutical history, as noted above, confined to the approved product. Neither research reagent has human data of its own.
What the literature has not shown
The research reagents have not been shown to be safe or effective for any use in people, and the online discussion of both compounds is overwhelmingly about human use that the literature does not support. MT-2 in particular is associated with regulatory warnings precisely because it is sold and used outside any approved framework. A research supplier can confirm identity and purity; the rest of the discussion is outside what a supplier can or should address.
How they are supplied for research
Quantum Peptides supplies Melanotan II, 10 mg and PT-141, 10 mg, both as lyophilized powder. Each lot is tested by an independent US laboratory to a minimum of 99% purity by HPLC, with mass-spectrometry identity, and the certificate is linked on each product page. The mass-spectrometry result is the practical way to tell the two apart: they differ by one mass unit (≈1,024.2 against ≈1,025.2), which a modern instrument resolves. Because tryptophan oxidises, also look for any +16 Da peak. See how to read a certificate of analysis.
Reconstitution and handling
Both dissolve readily in water or bacteriostatic water. As an example, 10 mg in 2 mL gives 5 mg/mL; the peptide calculator and reconstitution guide cover the arithmetic and procedure. The lactam ring, D-phenylalanine and norleucine substitutions make both peptides resistant to proteases and more stable in solution than most linear peptides of their size. The weak point is the tryptophan, which oxidises and is light-sensitive: keep solutions cold (2–8 °C) and in the dark, in amber or foil-wrapped vials, and freeze single-use portions for longer storage. Store the powder at −20 °C, desiccated and protected from light; see peptide storage and shelf life and bacteriostatic vs sterile water.
Frequently asked questions
What is the difference between Melanotan II and PT-141?
One terminal group. MT-2 ends in an amide (–NH2); PT-141 is the same cyclic peptide with a free carboxylic acid (–OH). PT-141 is the metabolite of MT-2, and the change shifts the receptor profile slightly.
What are the CAS numbers and molecular weights?
Melanotan II: CAS 121062-08-6, ≈1,024.2 g/mol. PT-141: CAS 189691-06-3, ≈1,025.2 g/mol.
What receptors do they act on?
Both are non-selective agonists at melanocortin receptors MC1R, MC3R, MC4R and MC5R, with negligible activity at MC2R. PT-141’s research use centres on MC4R and MC3R.
Why are these peptides stable in solution?
The cyclic lactam bridge, the D-amino acid at position 7 and norleucine in place of methionine all block the enzymes that degrade linear α-MSH. Tryptophan oxidation is the remaining weak point.
Is Melanotan II approved anywhere?
No. It has no regulatory approval, and several national regulators have warned against its unregulated sale for human use.
Can I buy Melanotan II or PT-141 for human use?
No. Quantum Peptides products are supplied for in-vitro and preclinical laboratory research only, not for human or veterinary use.
References
- Al-Obeidi F, Castrucci AM, Hadley ME, Hruby VJ. Potent and prolonged acting cyclic lactam analogues of α-melanotropin: design based on molecular dynamics. Journal of Medicinal Chemistry. 1989.
- Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006.
- Haskell-Luevano C, Sawyer TK, Hendrata S, et al. Truncation studies of α-melanotropin peptides identify tripeptide analogues exhibiting prolonged agonist bioactivity. Peptides. 1996.
Quantum Peptides supplies lyophilised research peptides for in-vitro and preclinical laboratory research only. Products are not for human or veterinary use. This guide summarises published literature and is not guidance on administration of any kind.