Melanotan II Research, Specifications & Scientific Information

Introduction

Melanotan II came out of the same University of Arizona programme that produced Melanotan I, and it is the more chemically interesting of the two: a ring, closed by a lactam bridge, holding the melanocortin message sequence in a fixed conformation. That constraint is what made it, in the words of its first clinical report, a superpotent melanotropic peptide ^[1].

It is also a compound whose development stopped. Its indexed human record is four small studies published between 1996 and 2000, involving fewer than fifty people in total, from one research group ^{[1, 2, 3, 4]}. No trial of it is registered on ClinicalTrials.gov. It has never been approved in any jurisdiction. The molecular scaffold went on to a different compound — PT-141, bremelanotide — which was developed through phase 3 and approved; this one was not.

What appeared in the literature afterwards is of a different kind: dermatology case reports describing people who obtained unlicensed material sold under the name, in which the substance administered was never characterised ^{[6, 7]}. This page reports the trial record and the case-report record as the separate things they are.

What Is Melanotan II?

Melanotan II is a synthetic cyclic heptapeptide. The structure recorded in its first clinical report is Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 alpha-MSH(4-10)-NH2 ^[1] — that is, the 4–10 fragment of alpha-melanocyte-stimulating hormone with three modifications:

• A lactam bridge between the aspartate side chain at position 5 and the lysine side chain at position 10, closing the molecule into a ring.
• Norleucine at position 4 in place of methionine, removing the residue most readily oxidised in the native hormone.
• D-phenylalanine at position 7, inverting the stereochemistry inside the His-Phe-Arg-Trp message sequence that every melanocortin shares.

The ring is the defining feature. A short linear peptide samples many conformations; a cyclised one samples few, and if the constrained conformation is the binding one, potency rises sharply. That is the design logic, and the in vitro potency reported for this molecule is the result of it.

PubChem carries it under compound identifier 92432, with CAS registry number 121062-08-6 and FDA/NCATS UNII code UPF5CJ93X7.

It has never held a marketing authorisation anywhere. It is not approved by the U.S. Food and Drug Administration for any indication, and no marketing application for it is on record in the United States.

Melanotan II Specifications

The structure recorded in the first clinical report is Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 alpha-MSH(4-10)-NH2, a cyclic heptapeptide in which a lactam bridge between the aspartate at position 5 and the lysine at position 10 closes a ring around the melanocortin message sequence. Three features distinguish it from the native hormone fragment: the ring itself, the norleucine substitution that removes the oxidation-labile methionine, and the D configuration at phenylalanine. PubChem carries it under compound identifier 92432 with CAS registry number 121062-08-6 and the FDA/NCATS UNII code UPF5CJ93X7; an acetate salt form carries a separate UNII, WYE6CXB7CH, and reagent material is commonly an acetate whose mass differs from the free-peptide figure. Neither the D configuration at phenylalanine nor the lactam ring can be confirmed by mass alone: the all-L linear peptide of the same composition would give the same nominal mass, and the two are different pharmacological entities.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Melanotan II Work?

It is a non-selective melanocortin receptor agonist ^[3], and that phrase carries most of what there is to say about its pharmacology.

The melanocortin receptors are five class A G protein-coupled receptors, MC1R through MC5R, that all signal through Gs and cyclic AMP. They sit in tissues with almost nothing in common: MC1R on melanocytes in the skin, MC2R in the adrenal cortex, MC3R and MC4R on neurons through the central nervous system, MC5R in exocrine tissue. What they share is the agonist recognition motif — the His-Phe-Arg-Trp core — which is precisely the part of the molecule this compound is built around.

The consequence is structural rather than incidental. A peptide built on the shared recognition sequence has no basis for discriminating between receptors that recognise it by that sequence, and engineering selectivity into this family has been correspondingly difficult across the whole field. Every published human observation on this compound is therefore an observation about simultaneous activation of receptors in several tissues, not about one of them.

No receptor-subtype potency ordering for this specific molecule was located in a primary source, and none is asserted here. What the literature does state is that it is non-selective ^[3] and that it is markedly more potent in vitro than the native hormone ^[1].

Melanotan II Mechanism of Action

In vitro research

Potency relative to the native hormone. The compound was characterised before its first clinical study as having superpotent melanotropic activity in cell-based assay, which is the property the cyclisation was designed to produce ^[1].

Non-selectivity across the receptor family. The investigators describe it as a non-selective melanocortin receptor agonist ^[3], which is the pharmacological premise underlying every observation in their human studies.

Where the scaffold went. Reviews of melanocortin peptide development trace the line from the native hormone through this cyclic analogue to the compounds that entered later-stage development ^[5]. The molecular work that produced this compound is better understood as a step in a programme than as a finished characterisation of it: the detailed receptor and structural pharmacology in this family was done later, on the compounds that were carried forward.

Findings in this section were obtained in cell-based receptor assays. Nothing in them establishes anything about intact animals or about humans.

What Is Melanotan II Being Researched For?

Nothing currently. No study of the compound is registered, and no primary research report on it has appeared since the early 2000s.

The research it was the subject of, between 1996 and 2000, covered:

• Tolerability and pigmentary response in healthy volunteers — the pilot phase 1 study ^[1].
• Erectile dysfunction — two small double-blind placebo-controlled crossover studies, in men with psychogenic and with organic causes ^{[2, 4]}, reviewed together by the investigators ^[3].

What has appeared since is case-report literature in dermatology journals, concerning material obtained outside any regulated supply chain ^{[6, 7]}. That is a literature about a market, not about a characterised substance.

None of this research is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Melanotan II

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Pilot phase 1 study, 1996

Design. A single-blind, alternating-day study in healthy male volunteers, beginning at 0.01 mg/kg subcutaneously and given daily Monday to Friday for two consecutive weeks. Two subjects were escalated in 0.005 mg/kg increments to 0.03 mg/kg and one to 0.025 mg/kg ^[1].

Result as reported. Two subjects showed increased pigmentation in the face, upper body and buttock one week after administration ended, measured both by quantitative reflectance and by visual assessment. The authors conclude that the compound has tanning activity in humans after five low amounts given every other day by subcutaneous injection ^[1].

Adverse effects. Mild nausea at most amounts given. At 0.03 mg/kg, grade II somnolence and fatigue in one of two subjects by World Health Organization criteria. A stretching and yawning complex appeared to correlate with the onset of spontaneous erections, which were experienced intermittently for one to five hours after administration ^[1].

Limitations. A pilot study in a handful of volunteers, single-blind rather than double-blind, with pigmentation assessed in two subjects. The authors' own conclusion is a recommendation for the amount to use in future phase 1 studies — the language of a programme at its beginning, not of a result.

Crossover studies in erectile dysfunction, 1998 and 2000

Population and design. Ten men with erectile dysfunction of no known organic cause in the first study, in a double-blind placebo-controlled crossover design with real-time RigiScan monitoring over six hours ^[2]. A companion study examined men with organic erectile dysfunction ^[4]. The investigators' combined review covers 20 men across the programme ^[3].

Result as reported. Clinically apparent erections developed in 8 of 10 men in the first study, with mean duration of tip rigidity above 80% of 38.0 minutes against 3.0 minutes on placebo (p = 0.0045) ^[2]. Across the 20 men, erection occurred in 17 in the absence of sexual stimulation, with a mean of 41 minutes of tip rigidity above 80%, and increased sexual desire was reported after 13 of 19 active administrations (68%) against 4 of 21 placebo administrations (19%), p < 0.01 ^[3].

Adverse effects. Nausea and yawning were frequently reported. At 0.025 mg/kg, 12.9% of subjects experienced severe nausea ^[3]. Transient nausea, stretching and yawning, and decreased appetite were reported more often on the active compound than on placebo in the first study, though none required treatment ^[2].

Limitations. Twenty men in total, from one group, with a physiological endpoint measured over six hours and no follow-up. The investigators' own conclusion was that the findings warrant further investigation of melanocortin agonists and antagonists — and the further investigation that followed was of other molecules, not this one.

The case-report literature

What it consists of. Reports in dermatology journals of pigmentary lesions in people who obtained injectable melanotropic peptides sold over the internet. A 2012 report describes melanoma in situ associated with such material and records that these compounds are unlicensed with an unproven safety record, and that reports of dysplastic naevi and melanoma associated with melanotropic peptides had already appeared ^[6]. A 2013 report describes atypical melanocytic naevi following injection ^[7].

How much weight it carries. Individual case reports establish temporal association, not causation, and the population reporting them is not a studied cohort. They carry one certainty, however: the substance in those cases was not analytically characterised, was not obtained through a regulated channel, and is not the material used in the 1990s studies above. A page that presented the trial data and the case reports as evidence about a single thing would be wrong about both.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Melanotan II vs Related Compounds

Against Melanotan I

Melanotan I is afamelanotide — a linear thirteen-residue analogue of the full hormone, and the active substance of a controlled-release implant approved in the United States and the European Union for one rare photodermatosis. This compound is a cyclic heptapeptide with no approval anywhere. They share a name, an origin and a message sequence; they do not share a structure, a development history or an evidence base.

Against PT-141

PT-141 (bremelanotide) is the same cyclic scaffold with the C-terminal lysine amide replaced by a free acid, a change that shifts the receptor potency profile. That compound was carried through phase 3 trials enrolling more than a thousand participants and a product containing it is approved in the United States for one indication in one population. The difference in outcome between two molecules this similar is a demonstration of how little structural similarity implies.

Against the native hormone

Alpha-MSH itself is cleared within minutes and is not a practical research tool. The cyclisation, the norleucine and the D-phenylalanine exist to address that, and they are the reason this compound exists at all.

Regulatory position

Approval in the melanocortin family is held by two specific finished products for two specific indications. Neither is this compound, and neither approval extends to it. Approval in the United States is specific to a compound, a product and an indication, and does not extend across a pharmacological class.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

Melanotan II is a cyclic heptapeptide with molecular formula C50H69N15O9 and average mass 1024.2 g/mol under PubChem compound identifier 92432.

Mass cannot confirm the molecule. Three of its defining features are invisible to a mass measurement. The lactam bridge between Asp5 and Lys10 costs one molecule of water relative to the open chain — a difference of 18 daltons, which is detectable, but an incompletely cyclised preparation and a correctly cyclised one differ by exactly that and are otherwise identical in composition. The D configuration at phenylalanine is identical in mass to the L form. And the acetyl and amide caps are the only charge-state clues an ordinary method has. A certificate reporting a mass consistent with 1024.2 daltons is consistent with the intended molecule and with several related substances that are not it.

The sequence cannot be written in single-letter code. Position 4 is norleucine, which has no single-letter representation; position 7 is a D residue, which single-letter code cannot express; and the cyclisation is a connectivity, not a residue. Any listing giving this compound as a plain capital-letter string is describing something else.

Cyclisation is the hardest step to get right. Side-chain-to-side-chain lactam formation competes with intermolecular reaction, so cyclic dimers and higher oligomers are the characteristic impurity class. They differ from the target by whole multiples of its mass and are readily detected if looked for, and readily missed if the method only confirms that the expected mass is present.

One tryptophan, which is both the chromophore and the liability. The single indole gives the molecule usable absorbance at 280 nm. It is also the residue most vulnerable to oxidation and photodegradation, and its oxidation products are close in mass to the parent and often poorly resolved from it.

Salt form. An acetate form carries its own UNII, WYE6CXB7CH, and reagent material is commonly an acetate or trifluoroacetate salt. A mass or purity figure that does not state the counter-ion and water content is incomplete.

Frequently Asked Questions

Scientific References

1. Dorr RT, Lines R, Levine N, et al.. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study Life sciences; 1996. PMID 8637402 doi:10.1016/0024-3205(96)00160-9
2. Wessells H, Fuciarelli K, Hansen J, et al.. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study The Journal of urology; 1998. PMID 9679884
3. Wessells H, Levine N, Hadley ME, et al.. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II International journal of impotence research; 2000. PMID 11035391 doi:10.1038/sj.ijir.3900582
4. Wessells H, Gralnek D, Dorr R, et al.. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction Urology; 2000. PMID 11018622 doi:10.1016/s0090-4295(00)00680-4
5. Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization Peptides; 2006. PMID 16412534 doi:10.1016/j.peptides.2005.01.029
6. Ong S, Bowling J. Melanotan-associated melanoma in situ The Australasian journal of dermatology; 2012. PMID 22724573 doi:10.1111/j.1440-0960.2012.00915.x
7. Reid C, Fitzgerald T, Fabre A, et al.. Atypical melanocytic naevi following melanotan injection Irish medical journal; 2013. PMID 23914578

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.