Melanotan-2 research vial
Sequence length
7 AA
Molecular weight
1024.18 g/mol
Current batch
MELAN202606
Dermal · Melanocortin receptor pharmacology / Pigmentation research

Melanotan-2

Cyclic heptapeptide α-MSH analog and non-selective melanocortin receptor agonist

Melanotan-2 (10mg vials)

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Specifications

Molecular weight1024.18 g/mol
Sequence length7 amino acids
Amino acid sequenceAc-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2
AppearanceWhite lyophilized powder
SolubilityBacteriostatic water; sterile water
Storage (lyophilized)-20°C, protected from light
Storage (reconstituted)2–8°C, use within 28 days
Half-lifeReported plasma half-life of approximately 30 minutes in published animal pharmacokinetic work
Current batch purity99.44% (HPLC) · MELAN202606

Melanotan-2 (MT-2, also written MT-II) is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH), designed at the University of Arizona by Hruby, Hadley, and colleagues in the late 1980s. The sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 contains a side-chain-to-side-chain lactam bridge between Asp and Lys that constrains the molecule into a ring, yielding markedly greater metabolic stability and receptor potency than linear α-MSH. MT-2 is a non-selective agonist at melanocortin receptors MC1R, MC3R, MC4R, and MC5R, and has been studied in vitro and in animal models for melanogenesis, MC4R-mediated signaling, and as the chemical parent of the FDA-approved derivative PT-141 (bremelanotide). MT-2 itself is not approved by the FDA for any human use and is supplied by NovaWell as a lyophilized powder, third-party tested for purity and endotoxin conformance, for laboratory research use only.

Research Studies

The following studies are summarized for educational purposes only. Inclusion does not imply any human use; all referenced research was conducted in vitro, in animal models, or under research protocols described in the original publications.

Research study

Design of a new class of superpotent cyclic α-melanotropins based on quenched dynamic simulations

Al-Obeidi F, Hadley ME, Pettitt BM, Hruby VJ. Journal of the American Chemical Society. 1989;111(9):3413–3416. View source ↗

Scientific findings

This is the foundational design paper describing the rational, computationally-guided construction of a cyclic lactam class of α-melanotropin analogs at the University of Arizona. Using quenched dynamic simulations to identify a low-energy conformation of the α-MSH message sequence, the authors designed a series of side-chain-to-side-chain lactam-bridged heptapeptides — including the compound that became known as Melanotan-II — in which Asp and Lys residues are covalently linked to constrain the backbone. In the classical frog skin (Rana pipiens) and lizard skin (Anolis carolinensis) melanocyte bioassays, the cyclic lactam analogs displayed melanotropic potencies several orders of magnitude greater than native α-MSH, with prolonged biological activity attributed to resistance to enzymatic degradation. The work established the structural template for the entire downstream class of cyclic melanocortin agonists, including PT-141 (bremelanotide) and afamelanotide.

Plain English

Scientists at the University of Arizona used computer simulations to figure out the best three-dimensional shape for a melanocortin-stimulating molecule, then built that shape into a small ring-shaped peptide. The ring locks the molecule into a single active conformation and protects it from being broken down by enzymes. In frog and lizard skin tests — standard tools for measuring melanocyte activity at the time — the resulting compound, Melanotan-II, was hundreds to thousands of times more active than the body's natural α-MSH. This paper is the chemistry blueprint that every later melanocortin compound, including the FDA-approved bremelanotide, was built on.

Research study

Evaluation of Melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study

Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME. Life Sciences. 1996;58(20):1777–1784. View source ↗

Scientific findings

This pilot phase-I trial — conducted at the University of Arizona by the same group that designed the molecule — evaluated subcutaneous MT-II in three healthy adult male volunteers under a single-blind, placebo-alternating protocol at a starting dose of 0.01 mg/kg administered Monday through Friday for two consecutive weeks. Quantitative reflectance measurements and visual scoring documented increased pigmentation of facial, upper-body, and gluteal skin in two of three subjects, persisting one week after the dosing period ended. The investigators recorded dose-related nausea, facial flushing, and spontaneous penile erections as the principal adverse events, with the erectogenic effect appearing 1–5 hours post-injection and correlating with a stretching-and-yawning complex. This paper is the most-cited primary human pharmacology source for MT-II and is the observation that directly motivated the spin-off development of bremelanotide (PT-141) as a melanocortin-targeted compound for sexual response research.

Plain English

The Arizona team gave low subcutaneous doses of MT-II to three healthy adult volunteers over two weeks and measured what happened. Skin in sun-exposed and non-sun-exposed areas got measurably darker in two of the three subjects, and the effect outlasted the dosing period by at least a week. The investigators also noted, unexpectedly, that MT-II produced spontaneous erections in the male volunteers — an observation that surprised the team and eventually led another group to develop PT-141 (bremelanotide), a closely related molecule, as a separate research compound focused on the sexual-response side of melanocortin pharmacology rather than on pigmentation.

Storage & handling

Lyophilized (unreconstituted): Store at -20°C, protected from light. Stable for 24+ months under correct storage. Avoid repeated temperature cycling.

Reconstituted: Dissolve in bacteriostatic water (typically 1–2 mL per 10 mg vial, depending on the research protocol). Store reconstituted solution at 2–8°C and use within 28 days. Do not freeze reconstituted solution. Protect from prolonged light exposure — the indole side chain of the tryptophan residue is photosensitive.

Vial format: 10 mg lyophilized, vacuum-sealed glass vial with rubber stopper and aluminum crimp. Sterility tested per USP guidelines.

Shipping: Lyophilized MT-2 is stable at ambient temperature for the typical 1–3 day shipping window. Cold-pack shipping available on request.

Frequently asked questions

What peptide sequence is Melanotan-2?+

Melanotan-2 is the cyclic heptapeptide Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, with a molecular weight of approximately 1024.18 g/mol (CAS 121062-08-6). It carries an N-terminal acetyl cap, a C-terminal amide, and a side-chain-to-side-chain lactam bridge formed between the carboxyl group of Asp and the ε-amino group of Lys. The seven residues correspond to a constrained, ring-locked version of the α-MSH "message sequence" (positions 4–10 of native α-MSH), with Met replaced by norleucine (Nle) for oxidative stability and L-Phe replaced by D-Phe for receptor selectivity and potency.

How is MT-2 different from MT-1 (afamelanotide)?+

MT-1 (also called Melanotan-I or afamelanotide) is a different molecule: a linear 13-amino-acid α-MSH analog with the sequence Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. MT-2, by contrast, is a cyclic 7-amino-acid molecule. MT-1 is the active ingredient in Scenesse, an implant approved by the FDA for use in adults with erythropoietic protoporphyria; it is much more selective for MC1R. MT-2 is non-selective across MC1R, MC3R, MC4R, and MC5R, is not FDA-approved for any use, and is investigational only.

How is MT-2 different from PT-141 (bremelanotide)?+

PT-141 (bremelanotide) is a close chemical derivative of MT-2. Both are cyclic heptapeptides built on the same Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys] scaffold, but PT-141 has a free C-terminal carboxylic acid (-OH) where MT-2 has a C-terminal amide (-NH2). PT-141 emerged after the Arizona team's 1996 pilot study showed that MT-2 induced spontaneous erections in male volunteers — Palatin Technologies developed the deaminated analog as a research compound focused on melanocortin-driven sexual response rather than pigmentation. PT-141 was approved by the FDA in 2019 for hypoactive sexual desire disorder in premenopausal women under the brand name Vyleesi. MT-2 itself remains investigational and is not approved for any human use.

What is the mechanism of action being studied?+

Melanotan-2 is a non-selective agonist at all four functional melanocortin receptors: MC1R (expressed on melanocytes, where activation stimulates eumelanin synthesis), MC3R and MC4R (expressed in the central nervous system, involved in energy balance, feeding behavior, and sexual response), and MC5R (expressed in exocrine glands and other peripheral tissues). The combination of N-acetylation, C-terminal amidation, Nle substitution, D-Phe inversion, and the Asp-Lys lactam bridge gives MT-2 substantially greater receptor potency and metabolic stability than native α-MSH, which is the chemistry rationale for its use as an investigational tool compound in melanocortin pharmacology.

What does NovaWell test MT-2 for?+

Every batch of Melanotan-2 supplied by NovaWell is tested by an independent third-party laboratory for: identity and purity (HPLC + MS), bacterial endotoxin (USP <85>), heavy metals (USP), and sterility (USP). The Certificate of Analysis for the currently shipping batch is linked from the Certificates tab on this page, along with the test date, manufacturer ID, and the independent laboratory that performed the analysis. Recent batches have tested above 99% pure by HPLC.

How should MT-2 be stored after reconstitution?+

Once reconstituted in bacteriostatic water, MT-2 should be stored at 2–8°C and used within 28 days. Do not freeze the reconstituted solution. Keep it protected from prolonged light exposure because the tryptophan residue in the ring is photosensitive. The lyophilized powder is stable at -20°C for 24+ months when protected from light.