Melanotan II: Research Reference

Melanotan II is a synthetic cyclic heptapeptide, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, designed at the University of Arizona in the late 1980s as a shortened, ring-closed analogue of alpha-melanocyte-stimulating hormone (alpha-MSH). A lactam bridge joins the side chains of its aspartic acid and lysine, and that ring, together with a D-phenylalanine, is what makes it far more potent and longer acting than the natural hormone.

This reference collects what a laboratory needs to know about Melanotan II as a material: how its ring and its seven residues behave in the vial, what it dissolves in, how it is handled at the bench and what to do when an order arrives. Each section below has its own page.

Molecular reference

Name	Melanotan II
Also known as	MT-II, MT-2, Melanotan-II
Sequence	Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (lactam bridge between Asp2 and Lys7; Nle = norleucine)
Residues	7
Molecular formula	C50H69N15O9
Molecular weight	1024.2 g/mol
CAS number	121062-08-6

Formula, molecular weight, CAS number and synonyms are from PubChem (CID 92432). The MedChemExpress data sheet (HY-P0267) gives the same formula and CAS number, a weight of 1024.18 and the sequence written as Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-NH2, (2→7)-lactam.

Three features of that structure explain most of its behaviour. The ring and the D-phenylalanine make it resistant to enzymes; its developers describe it as one of a group of superpotent, prolonged-acting, enzymatically resistant melanocortin analogues (Hadley and Dorr, Peptides, 2006). The norleucine at its start sits where alpha-MSH carries a methionine (Al-Obeidi et al., Journal of Medicinal Chemistry, 1989); norleucine has no sulfur, so the commonest oxidation route in peptides is designed out. And it keeps a tryptophan and a histidine, both of which can oxidise (Li et al., Biotechnology and Bioengineering, 1995), with tryptophan the one that reacts to light. Light, air and warmth are therefore the things to manage.

What it is studied for

Melanotan II came out of a design programme based on molecular dynamics. Closing alpha-MSH fragments into lactam rings of different sizes showed that a 23-membered ring, the size in Melanotan II, gave about 90 to 100 times the potency of alpha-MSH in a lizard skin bioassay, with prolonged activity, while larger or smaller rings were weaker (Al-Obeidi et al., 1989). It binds several melanocortin receptors; the Cayman Chemical sheet lists it as an agonist of MC1R, MC3R, MC4R and MC5R, citing receptor binding work in cells expressing the human receptors (Cayman Chemical, item 27316).

In a single-blind, placebo-controlled pilot phase I study in three healthy male volunteers, two showed increased pigmentation of the face and upper body a week after the last administration, measured by reflectance, and the study recorded side effects including mild nausea and, in one subject, somnolence and fatigue (Dorr et al., Life Sciences, 1996). Its developers later reviewed its clinical testing for skin tanning and male sexual function, and the related analogue PT-141 came out of that work (Hadley and Dorr, 2006). In animal research it has been studied on appetite, energy balance and nerve regeneration, the areas cited on the supplier’s sheet.

Our summaries are in what is Melanotan II, Melanotan II clinical history and PT-141 and PT-141 vs Melanotan II.

Stability

With no methionine, cysteine, asparagine or glutamine, and a ring that resists enzymes, Melanotan II is sturdier than most peptides of its size. Its slow route in solution is oxidation of the tryptophan, which light speeds up, with histidine oxidation behind it. The Melanotan II stability page covers those routes, the lactam ring, freeze-thaw and what visible changes mean.

Solubility

Melanotan II dissolves in water, where one supplier rates it at 100 mg/mL or more, but another calls its acetate salt sparingly soluble in neutral buffer. The Melanotan II solubility guide explains why those two figures differ, why bacteriostatic water is the right solvent and what causes haze.

Handling

Bench practice for Melanotan II is mostly about keeping the solution cold, dark, sealed and labelled. The Melanotan II handling page lists the steps, the spray and the common mistakes.

On arrival

What a sealed vial should look like, why it travels without an ice pack and where it goes first are on the Melanotan II on-arrival page.

Storage and reconstitution

Fridge and freezer windows, before and after mixing, are on how long Melanotan II lasts. Water volumes and the concentration table for a 10 mg vial are on how much bacteriostatic water for a Melanotan II 10 mg vial.

FAQ

Short answers to the questions researchers ask most about storing, mixing and handling Melanotan II are on the Melanotan II FAQ.

Where to get it

Vistara Labs supplies Melanotan II 10 mg as a lyophilised vial for laboratory research, shipped within Canada by Canada Post Xpresspost. A ready-mixed Melanotan II Nasal Spray is also available. Certificates are on our lab reports page.