Peptide · Research Monograph · Cyclic heptapeptide melanocortin (α-MSH) analog

Melanotan II

Melanin Production Studies

Melanotan II is a ring-shaped version of alpha-MSH, a hormone that signals pigment production. Closing the molecule into a ring makes it far more stable than the natural hormone. Studies have measured melanin production in pigment cell cultures and mapped which melanocortin receptors it binds and how strongly.

For laboratory research use only - not for human or animal use

Molecular data

Molecular formulaC50H69N15O9
Molecular weight1024.18 Da
SequenceAc-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2
Sequence length7 residues
CAS / identifierMelanotan II (MTII)
Physical formLyophilized Powder
Available sizes10mg

How it works

MC1R Agonism

MC1R Signalling & Melanogenesis

Melanotan II (MTII) activates MC1R on melanocytes, with intracellular cAMP production and melanogenesis — the synthesis of eumelanin (brown-black) pigment — measured downstream. This mechanism is studied as a model for UV-independent pigmentation and photoprotection pathways.

  • Potent MC1R agonism drives eumelanin synthesis
  • Activates adenylyl cyclase/cAMP/PKA signaling cascade
  • Melanin production measured without UV exposure in models
MC4R Agonism

Central MC3R / MC4R Pathways

MTII's high-affinity binding at MC4R in the hypothalamus acts on both feeding-related and arousal-related signalling. MC4R knockout studies show these pathways are distinct. Its non-selective binding at MC3R and MC4R makes it a pharmacological tool for dissecting melanocortin circuits in energy balance research.

  • MC4R activation suppresses food intake in animal models
  • Modulates hypothalamic energy expenditure circuits
  • Precursor to the more selective PT-141 (bremelanotide)
Receptor Selectivity

Non-Selective Pan-MC Agonism

Unlike its derivative PT-141, Melanotan II is a non-selective melanocortin receptor agonist that activates MC1R through MC5R with varying affinities. This broad receptor activity makes it uniquely valuable as a pharmacological probe for studying the full melanocortin system in preclinical research, while also contributing to its broader side-effect profile.

  • Binds MC1R, MC3R, MC4R, and MC5R
  • ~1000× more potent than endogenous α-MSH at MC receptors
  • Cyclic D-Phe substitution confers metabolic resistance

What the research shows

Pigmentation

Melanogenesis Research

Research into MC1R-driven melanin synthesis, including UV-independent pigmentation and photoprotection models. Used as a pharmacological tool to dissect melanocyte signalling pathways and study disorders of pigmentation.

Energy Balance

Melanocortin Energy Balance

MTII is a key pharmacological tool in metabolic and energy-homeostasis research. In rodent models, MC4R activation is associated with lower food intake and higher energy expenditure; used extensively to validate the melanocortin hypothesis.

MC4R Signalling

Arousal Pathway Models

Preclinical research using MTII as a non-selective MC agonist probe contributed to the discovery of melanocortin-mediated arousal pathways, eventually leading to the development of PT-141 (bremelanotide) as a more selective MC4R-focused compound.

Receptor Pharmacology

Melanocortin System Probing

As a potent non-selective MC receptor agonist, MTII serves as a pharmacological tool for receptor binding studies, structure-activity relationship (SAR) research, and comparison of downstream signaling cascades across the five melanocortin receptor subtypes.

Specification

Chemical NameMelanotan II (MTII)
SequenceAc-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂
Molecular Weight1024.18 Da
Molecular FormulaC₅₀H₆₉N₁₅O₉
FormLyophilized powder
Purity≥99% (HPLC verified)
TestingThird-party HPLC, Mass Spec, Endotoxin
Storage-20°C for long-term stability
SolubilityWater or bacteriostatic water
COAIncluded with every order

Frequently asked questions

What is Melanotan II?

Melanotan II (MTII) is a synthetic cyclic heptapeptide analog of alpha-melanocyte stimulating hormone (α-MSH). It was originally developed at the University of Arizona in a research programme on synthetic melanocortins for pigmentation and photoprotection. MTII activates melanocortin receptors (MC1R through MC5R) with higher potency than endogenous α-MSH, making it a pharmacological research tool for the melanocortin system.

How does Melanotan II differ from PT-141 (Bremelanotide)?

PT-141 (bremelanotide) is derived from Melanotan II through chemical modification. The difference is selectivity: Melanotan II is a non-selective agonist at MC1R, MC3R, MC4R and MC5R, with broader downstream activity including melanogenesis. PT-141 was engineered for narrower selectivity toward MC4R with reduced MC1R activity, so pigmentation activity is largely absent while central pathway activity remains.

Is Melanotan II approved for human use?

No. Melanotan II has not been approved by the FDA, EMA, or any regulatory authority for human use. It is classified as a research chemical with no approved indication. Regulatory agencies including the FDA and UK MHRA have issued warnings about unlicensed MTII products marketed for tanning. It is available here exclusively for legitimate in vitro research purposes.

What is the melanocortin system and why is MTII used to study it?

The melanocortin system consists of five G protein-coupled receptors (MC1R–MC5R) that respond to endogenous ligands including α-MSH, β-MSH, γ-MSH, and ACTH. This system regulates diverse functions including pigmentation (MC1R), adrenal steroidogenesis (MC2R), energy balance (MC3R, MC4R), and exocrine secretion (MC5R). MTII's high potency and non-selectivity across all MC receptors makes it an ideal pharmacological probe for pan-melanocortin system research and structure-activity relationship studies.

What safety concerns are associated with Melanotan II research?

Due to MTII's broad, non-selective receptor activity, researchers and regulatory agencies have raised concerns about potential effects on melanocytic nevi (moles) and theoretical melanoma risk through excessive MC1R stimulation. Early human pilot studies reported significant adverse events including nausea, yawning, and spontaneous erection from MC4R stimulation. No long-term safety data from controlled clinical trials exists. These considerations make careful research design essential when working with MTII.

How should research-grade Melanotan II be stored?

Lyophilized MTII should be stored at -20°C and protected from light and moisture. The cyclic structure with D-phenylalanine substitution provides greater proteolytic stability than linear α-MSH, but the material should still be handled and stored carefully to preserve receptor binding activity in research assays.

For laboratory research use only. Not a drug, supplement, or medical product; not for human or animal use. All findings referenced are from published preclinical/laboratory research.