Melanotan 1, Melanotan 2 and PT-141: alpha-MSH analogues and MC1R and MC4R receptors

Melanotan 1, Melanotan 2 and PT-141 belong to one peptide family, yet they differ in structure, receptor profile and the way they behave in the laboratory. This overview places them side by side, so that it is easier to choose the right compound for a specific research question.

Three molecules from one family

All three compounds are synthetic analogues of alpha-MSH, the naturally occurring melanocyte-stimulating hormone. Alpha-MSH is derived from proopiomelanocortin (POMC) and is one of the best described peptides in the melanocortin family. Its natural sequence contains 13 amino acid residues and, in research, serves as the reference point for the whole group of melanocortin receptors.

Analogues are created by modifying this sequence. The order of residues is changed, substituents are added or the molecule is closed into a ring. Each of these changes affects how the peptide behaves in solution and which receptors it interacts with. This is why Melanotan 1, Melanotan 2 and PT-141 are so often compared with one another in the literature.

Melanotan 1: a linear analogue and the MC1R receptor

Melanotan 1, also known as afamelanotide, is a linear peptide with the formula C78H111N21O19 and a molecular weight of 1646.9 g/mol. It keeps a structure close to alpha-MSH, with several modifications that increase its resistance to enzymatic breakdown. Its CAS number is 75921-69-6.

In vitro and in animal models, Melanotan 1 is described as an agonist of the MC1R receptor, which is found mainly on melanocytes, the cells that produce melanin. According to published descriptions, activation of this receptor triggers cAMP-dependent signalling and, in melanocyte cultures, leads to increased melanin synthesis. This selectivity is why Melanotan 1 is often chosen as a reference in research on melanocyte biology.

Melanotan 2: a cyclic analogue with a broad profile

Melanotan 2, also called Melanotan II, is a cyclic analogue of alpha-MSH with the formula C50H69N15O9 and a molecular weight of 1024.2 g/mol. Its ring forms through a bond between the aspartate and lysine residues. Restricting the flexibility of the molecule means it adopts a more defined spatial structure than its linear counterparts.

Melanotan 2 is a non-selective agonist of melanocortin receptors. In research descriptions it binds several subtypes: MC1R, MC3R, MC4R and MC5R. MC1R on melanocytes remains the most discussed pathway, but this broad affinity makes Melanotan 2 a convenient reference point. When a researcher wants to see how the whole receptor family responds, rather than a single subtype, this is often the compound reached for.

PT-141: a cyclic heptapeptide acting on MC3R and MC4R

PT-141, known as bremelanotide, is a cyclic heptapeptide with the formula C50H68N14O10 and a molecular weight of about 1025 g/mol. It was developed during research on Melanotan II and differs from it mainly at the C-terminal end. The sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH contains seven residues, and the ring is closed by an amide bond between aspartate and lysine.

In research descriptions PT-141 is an agonist of MC3R and MC4R, and also of MC1R. The MC4R receptor is analysed particularly often in the central nervous system, in animal models and in cell lines that express it. The preclinical literature on this compound is extensive, so it is worth reviewing before planning your own experiment.

Comparison in one place

Feature	Melanotan 1	Melanotan 2	PT-141
Molecule type	linear, 13 residues	cyclic, 7 residues	cyclic, 7 residues
Formula	C78H111N21O19	C50H69N15O9	C50H68N14O10
Molecular weight	1646.9 g/mol	1024.2 g/mol	about 1025 g/mol
Receptors described in research	MC1R	MC1R, MC3R, MC4R, MC5R	MC1R, MC3R, MC4R
Form in our shop	10 mg lyophilisate	10 mg lyophilisate	10 mg lyophilisate

The table shows that the difference is not limited to chain length. The type of ring and the set of receptors the molecule interacts with in a given model matter just as much.

Why structure matters in research

A linear peptide such as Melanotan 1 is more flexible. A cyclic peptide such as Melanotan 2 or PT-141 has a more rigid backbone. The literature often describes cyclic structures as more resistant to proteolytic enzymes, which cut peptides at their bonds. D-amino acid residues, present in Melanotan 2 and PT-141, play a similar role, because enzymes recognise them less readily than the natural L forms.

For a research project, this means the result of a comparison depends not only on the receptor, but also on how the molecule behaves in solution over the duration of the experiment. Stability is therefore a parameter worth controlling alongside activity.

How to plan a comparison

The most common setup is a cell culture expressing the chosen receptor subtype, with a cAMP read-out. All three compounds can be tested in the same concentration series, next to natural alpha-MSH as a reference and a solvent-only control. Such a design makes it possible to separate the receptor effect from random noise and from the influence of the vehicle.

Keeping the preparation of solutions identical is equally important. The same solvent batch, the same time from reconstitution to measurement and the same storage temperature reduce variability that could not be explained later by biology. Every project should define clear evaluation criteria before the first vial is opened.

When reading the literature, pay attention to several details: the type of model, the cell line, the method used to measure activity, and whether all results come from the same laboratory. Studies carried out on different cell lines rarely give directly comparable numbers, even when they describe the same receptor. That is why the most reliable comparisons come from experiments in which all three compounds are studied in parallel, under one protocol and by one team. Such a design is also easier to describe later in a publication or in the documentation of your own project.

Working in the laboratory

Store the lyophilisate at -20 °C, tightly sealed, away from light and moisture. Before opening a vial, let it reach room temperature to limit condensation of water vapour. Reconstitute immediately before use, in a solvent chosen for the planned experiment. After dissolving, keep the solution at 2-8 °C, divide it into portions and avoid repeated freezing and thawing.

Calculate working concentrations in advance with the concentration calculator. This way every point in the measurement series has a calculated value rather than an approximate one. Each MOLEVIA batch has a purity of at least 99%, confirmed by HPLC and MS. Orders are dispatched within 24 hours. InPost delivers parcels to Parcel Lockers in Poland, and DPD handles shipments across Europe.