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

Melanotan II

Studied for natural tanning and sexual arousal

Melanotan II is a melanocortin peptide researched for two effects in particular: stimulating the skin's natural tanning pigment (melanin) and activating sexual arousal pathways.

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

Available in the Eon catalog — Melanotan II from $45.00 Certificate of analysis (PDF)

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

Melanocyte Stimulation & Pigmentation

Melanotan II (MTII) activates MC1R on melanocytes, stimulating intracellular cAMP production that drives melanogenesis — the synthesis of eumelanin (brown-black) pigment. This mechanism has been extensively studied as a model for understanding UV-independent tanning and photoprotective pigmentation pathways.

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

Central Appetite & Arousal Pathways

MTII's high-affinity binding at MC4R in the hypothalamus modulates both appetite suppression and arousal-related signaling. MC4R knockout studies demonstrate these pathways are distinct. MTII's non-selective binding at MC3R and MC4R makes it a pharmacological tool for dissecting melanocortin circuit functions 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

Extensive research into MC1R-driven melanin synthesis, including UV-independent tanning mechanisms and photoprotection models. Used as a pharmacological tool to dissect melanocyte signaling pathways and study disorders of pigmentation.

Dorr et al. 1996

Energy Balance

Appetite & Metabolic Research

MTII is a key pharmacological tool in obesity and energy homeostasis research. MC4R activation reduces food intake and increases energy expenditure in rodent models; used extensively to validate the melanocortin hypothesis of body weight regulation.

Fan et al. 1997

Sexual Function

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.

Wessells et al. 1998

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.

Sawyer et al. 1993

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 (lyophilized)-20°C for long-term stability
Storage (reconstituted)2–8°C, use within 30 days
SolubilityWater or bacteriostatic water
COAIncluded with every order

Frequently asked questions

What is Melanotan II?

Melanotan II (MTII) is a synthetic cyclic heptapeptide and superpotent analog of alpha-melanocyte stimulating hormone (α-MSH). It was originally developed at the University of Arizona as part of a research program to create synthetic melanocortins for tanning and photoprotection. MTII activates melanocortin receptors (MC1R through MC5R) with substantially higher potency than endogenous α-MSH, making it a pharmacological research tool for studying the melanocortin system.

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

PT-141 (bremelanotide) is actually derived from Melanotan II through chemical modification. The key difference is selectivity: Melanotan II is a non-selective agonist activating MC1R, MC3R, MC4R, and MC5R, producing broader physiological effects including melanogenesis. PT-141 was engineered for improved selectivity toward MC4R with reduced MC1R activity, eliminating the tanning effect while retaining central arousal pathway activity.

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. Once reconstituted with bacteriostatic water, store at 2–8°C and use within 30 days. The cyclic structure with D-phenylalanine substitution provides greater proteolytic stability than linear α-MSH, but reconstituted peptide should still be handled and stored carefully to preserve receptor binding activity in research assays.

Literature

  • PubMed Melanocortins and Melanocortin Receptors 1993 · Sawyer TK et al.
  • PubMed Role of Melanocortinergic Neurons in Feeding and the Agouti Obesity Syndrome 1997 · Fan W et al.
  • PubMed Synthetic Melanotropic Peptide Initiates Erections in Men with Psychogenic Erectile Dysfunction 1998 · Wessells H et al.
  • PubMed Melanotan-II, a Potent Melanotropin and Erectogenic Agent 1996 · Dorr RT et al.

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.