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Cyclic melanocortin-receptor agonist (unlicensed research peptide)

Melanotan II

Melanotan II is a synthetic cyclic heptapeptide analogue of α-melanocyte-stimulating hormone (Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2) that non-selectively activates melanocortin receptors, producing skin darkening through MC1R and erections and appetite effects through MC4R.

By The Peptides Codex Editorial TeamReviewed September 8, 2026

Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.

Length
7 aa
Class
Cyclic melanocortin-receptor agonist (unlicensed research peptide)
Function
Non-selective melanocortin agonist: MC1R-driven skin pigmentation, MC4R-mediated erectile and appetite effects
Context
Not approved in any jurisdiction; sold unlawfully online as a tanning injectable. One phase 2 trial registered (2026) as an adjunct to phototherapy

A 1980s University of Arizona tanning peptide that never got a licence, acquired a black market, and is documented mainly through case reports of harm.

Also known as: MT-2 · MT-II · Melanotan 2 · MT2 · Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2

Part of the Cosmetic & skin peptides cluster

Overview

Melanotan II is a synthetic cyclic heptapeptide analogue of α-melanocyte-stimulating hormone (Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2) that non-selectively activates melanocortin receptors, producing skin darkening through MC1R and erections and appetite effects through MC4R. It has never been approved anywhere and is sold unlawfully online for tanning; the published human literature consists largely of case reports of rhabdomyolysis, renal infarction and melanoma coinciding with its use. A phase 2 trial as an adjunct to phototherapy was registered in 2026.

Source & context

Biological / chemical source: Synthetic cyclic peptide

Primary research or clinical context: Not approved in any jurisdiction; sold unlawfully online as a tanning injectable. One phase 2 trial registered (2026) as an adjunct to phototherapy

What Melanotan II is

Melanotan II (MT-II) is a synthetic cyclic peptide analogue of α-melanocyte-stimulating hormone, designed in the 1980s at the University of Arizona as a candidate sunless-tanning agent. Seven residues — norleucine, then a ring of Asp-His-D-Phe-Arg-Trp-Lys closed by a lactam bridge — reproduce the His-Phe-Arg-Trp core that every melanocortin receptor recognises, in a form far more potent and stable than the hormone. Formula C50H69N15O9, average mass about 1,024 Da. It was never licensed. Its C-terminal amide is the only difference from bremelanotide, which was later approved for a different indication; MT-II itself survives as an unlicensed injectable sold online for tanning.

Sequence and chemistry

The IUPHAR one-letter representation is XDHFRWK, where X is norleucine; the display cannot show the D-configuration of the phenylalanine or the ring closure between the aspartate and lysine side chains, both of which are what make the molecule work. Norleucine replaces α-MSH's methionine to remove an oxidation site; D-Phe at position 4 and the lactam constraint hold the pharmacophore in its active shape and protect it from peptidases. Medicinal-chemistry work continues on this scaffold — Tomassi et al. (Journal of Medicinal Chemistry 2022) used it to generate functionally selective melanocortin agonists — because the α-MSH core remains the template for the whole receptor family.

Mechanism and effects

MT-II activates melanocortin receptors without selectivity. At MC1R on melanocytes it increases eumelanin synthesis, hence skin darkening even without sun; at MC4R in the hypothalamus it triggers erections and suppresses appetite — in anaesthetised rats, intravenous or intra-hypothalamic MT-II dose-dependently induced erectile events (Giuliano et al., Neuroscience 2006). Rodent studies have explored other central effects: reversal of memory impairment after a high-fat diet (Wekwejt et al., Biomedicine & Pharmacotherapy 2023) and of autism-like behaviours in a maternal-immune-activation mouse model (Minakova et al., PLoS One 2019). These are laboratory findings with the peptide as a tool compound, not evidence for any human use.

Human evidence: case reports of harm

Because MT-II was never developed through trials, the human literature is dominated by adverse-event reports. A 39-year-old man who injected 6 mg — six times what he understood to be the starting dose — developed sympathomimetic toxicity and rhabdomyolysis with creatine kinase peaking at 17,773 IU/L and acute kidney injury, requiring intensive care (Nelson et al., Clinical Toxicology 2012). A 20-year-old woman with skin type II developed cutaneous melanoma three months after a course of self-injected MT-II combined with sunbed use (Hjuler et al., Dermatology 2014). Renal infarction attributed to MT-II has been reported, with thrombotic and direct toxic mechanisms proposed (Peters et al., CEN Case Reports 2020). Case reports cannot establish causation, but they define the risk profile that no trial ever measured.

Published case reports in the evidence pack
ReportEventContext
Nelson et al. 2012Rhabdomyolysis, tachycardia, kidney injury6 mg self-injection, internet-sourced
Hjuler et al. 2014Cutaneous melanoma3–4 week course plus sunbeds, skin type II
Peters et al. 2020Renal infarctionReview plus case; thrombotic mechanism proposed

How it is actually used

A qualitative study of UK and Irish online forums (Gilhooley et al., Dermatology 2021) extracted 623 discussion entries from 205 participants and found motivations centred on a tanned appearance before holidays and for fitness or bodybuilding, alongside widespread misinformation about an unregulated product, improvised preparation and dosing, sunbed use, and side effects. The covert nature of use means prevalence is unknown. Health authorities in several countries have issued warnings against injecting melanotan products bought online.

Regulatory status and a single trial

Melanotan II is not approved in any jurisdiction and cannot be lawfully sold for human use in the US, Canada or the EU. Its related compound afamelanotide (Melanotan I), a linear analogue, is an approved implant for a rare photosensitivity disorder, which is why the two names are often confused; the melanotan comparison guide separates them. In 2026 a phase 2 trial was registered (NCT07437560) testing MT-II as an adjunct to narrow-band UVB phototherapy for repigmentation, listed as recruiting — the first controlled human study of the molecule in decades.

What this page is not

It is an educational profile of a research peptide with a documented harm record and no approval. It does not describe how to obtain, prepare or use anything, and it is not medical advice.

Sequence

One-letter sequence commonly cited for Melanotan II (educational; isoforms and modifications may differ):

XDHFRWK

XDHFRWK

X = norleucine (Nle), a non-canonical residue; the D-Phe at position 4 and the Asp–Lys lactam bridge that closes the ring are not shown in one-letter code. X marks a non-canonical residue — see the structure block below. (Plotted as alanine on the wheel.)

Melanotan II7 aa · C50H69N15O9 · ≈ 1,024.2 Da · Amide (the des-amide form is bremelanotide)PEPTIDESCODEX.COMN-terminus →→ C-terminusX1D−2H3F4R+5W6K+7nonpolarpolaracidicbasicGly / Pronon-canonical (X)Hydropathy (Kyte–Doolittle): ▮ hydrophobic (cyan) / ▮ hydrophilic (rose) · Side-chain charge at pH 7: + / −X = norleucine (Nle), a non-canonical residue; the D-Phe at position 4 and the Asp–Lys lactam bridge that cl…
Melanotan II — Structure cardDownload SVG
A1D2H3F4R5W6K7
Helical wheel projection

Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.

Analyze sequences in the playground →

Structure & chemistry

Molecular identity & reference confidence

Source-supported reference

Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.

Molecular form
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 — a cyclic lactam-bridged analogue of the α-MSH core sequence His-Phe-Arg-Trp
Species
Not established by this molecular identity audit
Termini (N / C)
Not specified / Amide (the des-amide form is bremelanotide)

Average reference mass

Reference policy updated: 2026-10-05

Molecular formula
C50H69N15O9
Average reference mass
≈ 1,024.2
Receptors
Non-selective melanocortin agonist: MC1R (pigmentation), MC3R and MC4R (sexual function, appetite), MC5R
Backbone
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 — a cyclic lactam-bridged analogue of the α-MSH core sequence His-Phe-Arg-Trp
C-terminus
Amide (the des-amide form is bremelanotide)
Status
Not approved in any jurisdiction as of September 2026; one phase 2 trial registered (NCT07437560)
Chemical modifications (IUPHAR record)

Nle1 replaces the oxidisable Met of α-MSH; D-Phe4 and the side-chain lactam cyclisation between Asp and Lys lock the receptor-binding conformation and resist proteolysis; N-acetyl and C-amide cap the termini.

Identifiers

Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.

Clinical development snapshot

ClinicalTrials.gov lists 1 registered study with “Melanotan II” as an intervention (snapshot 2026-09-06). A registry footprint is not evidence of efficacy or approval.

Registered studies
1
Highest phase reached
Phase 2
Active in latest 100
1
Most recent update
2026-02-27
Most recently updated studies
NCTTitlePhaseStatusUpdated
NCT07437560Melanotan II (MT-II) as an Adjunct to NB-UVB Phototherapy for Repigmentation in Stable Nonsegmental VitiligoPhase 2recruiting2026-02-27
See all on ClinicalTrials.gov →
Concentration math

Melanotan II — reconstitution calculator

Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.

Reference form: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 — a cyclic lactam-bridged analogue of the α-MSH core sequence His-Phe-Arg-TrpAverage reference mass: 1,024.2 Da

Syringe graduation
Solution concentration
5 mg/mL5,000 mcg/mL
mcg

Enter an amount to see the volume it corresponds to.

Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.

Open the Melanotan II calculator on its own page →

Change log

Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.

  1. EditorialProfile content reviewed and updated by the editorial team.

FAQ about Melanotan II

What is Melanotan II?+

Melanotan II is a synthetic cyclic heptapeptide analogue of α-melanocyte-stimulating hormone (Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2) that non-selectively activates melanocortin receptors, producing skin darkening through MC1R and erections and appetite effects through MC4R. It has never been approved anywhere and is sold unlawfully online for tanning; the published human literature consists largely of case reports of rhabdomyolysis, renal infarction and melanoma coinciding with its use. A phase 2 trial as an adjunct to phototherapy was registered in 2026.

What Canadian product status is recorded for Melanotan II?+

Canadian product status for Melanotan II has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.

What is the typical length of Melanotan II?+

Melanotan II is commonly described as approximately 7 amino acids (Cyclic melanocortin-receptor agonist (unlicensed research peptide)).

What is Melanotan II?+

A synthetic cyclic analogue of α-MSH that activates melanocortin receptors non-selectively, causing skin darkening (MC1R) and erections and appetite changes (MC4R). It was never approved.

Is Melanotan II safe?+

Unknown — it was never tested in trials. The human literature is case reports: rhabdomyolysis and kidney injury after a 6 mg injection, melanoma coinciding with use plus sunbeds, and renal infarction.

Is Melanotan II legal or approved?+

It is not approved anywhere and cannot lawfully be sold for human use in the US, Canada or the EU. A phase 2 phototherapy-adjunct trial was registered in 2026.

What is the difference between Melanotan II and PT-141?+

One terminal group: MT-II is the C-terminal amide, bremelanotide (PT-141) the free acid. Bremelanotide is an approved medicine for a sexual-desire indication; MT-II is unlicensed.

What is the difference between Melanotan I and II?+

Melanotan I (afamelanotide) is a linear α-MSH analogue approved as an implant for a rare photosensitivity disorder; Melanotan II is a cyclic, non-selective analogue with no approval.

What is the sequence of Melanotan II?+

Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2; formula C50H69N15O9, mass about 1,024 Da.

Further reading

Related peptides

References & further reading

  1. 1.Todorovic et al. (2024). 5-Hydroxypyrroloindoline Affords Tryptathionine and 2,2'-bis-Indole Peptide Staples: Application to Melanotan-II. Chemistry
  2. 2.Wekwejt et al. (2023). Melanotan-II reverses memory impairment induced by a short-term HF diet. Biomed Pharmacother
  3. 3.Nelson et al. (2012). Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila)
  4. 4.Gilhooley et al. (2021). Melanotan II User Experience: A Qualitative Study of Online Discussion Forums. Dermatology
  5. 5.Tomassi et al. (2022). CLIPSing Melanotan-II to Discover Multiple Functionally Selective hMCR Agonists. J Med Chem
  6. 6.Peters et al. (2020). Melanotan II: a possible cause of renal infarction: review of the literature and case report. CEN Case Rep
  7. 7.Hjuler et al. (2014). Melanoma associated with the use of melanotan-II. Dermatology
  8. 8.Devlin et al. (2013). Melanotan II overdose associated with priapism. Clin Toxicol (Phila)
  9. 9.Giuliano et al. (2006). Melanotan-II: Investigation of the inducer and facilitator effects on penile erection in anaesthetized rat. Neuroscience
  10. 10.Minakova et al. (2019). Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism. PLoS One
  11. 11.PubChem — Melanotan II (CID 92432)
Disclaimer: Educational content only. Not medical advice. Not instructions for human use. Research peptides and unapproved products may be restricted or illegal to market for human consumption in your jurisdiction. Consult qualified professionals and applicable law.
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