en · de · es · fr · pt
methods-notes.peptides1126.com › Guide › Melanotan-2 Structure And Receptor Pharmacology — Background and Details

Melanotan-2 Structure And Receptor Pharmacology — Background and Details

By Editorial Desk · published 2025-12-19 · last reviewed 2026-01-10 · Guide

This is a working overview of melanocortin receptor, written for readers who want more than a one-paragraph summary but less than a textbook.

This page was last updated on 2026-01-10 and is reviewed periodically as new material appears.

Melanotan-2 Structure and Receptor Pharmacology

Melanotan-2 is a synthetic cyclic heptapeptide designed as a structural analogue of alpha-melanocyte-stimulating hormone, the endogenous tridecapeptide that regulates pigment production. Two modifications distinguish it from the natural hormone: norleucine replaces methionine at the N-terminus, which limits oxidation, and a D-phenylalanine substitution raises receptor affinity. The ring is closed through an aspartate-lysine lactam bridge, giving the molecule a constrained conformation. The free base has a molecular mass near 1024 daltons, and commercial material is usually supplied as an acetate salt. It appears in the literature as a research peptide rather than an approved therapeutic agent.

Receptor studies place melanotan-2 among non-selective melanocortin agonists, binding MC1R, MC3R, MC4R and MC5R rather than a single subtype. Activation of MC1R on cutaneous melanocytes raises tyrosinase activity and shifts pigment synthesis toward eumelanin, which is darker and more photostable than pheomelanin. Central receptors, particularly MC4R, are associated with appetite suppression and with reported effects on sexual function. Because subtype selectivity is low, the same molecule engages pigment, metabolic and vascular pathways at once, and this breadth is a common explanation offered for the range of adverse events described in user reports.

Melanotan-2 Identity and Receptor Pharmacology

Melanotan-2 is a synthetic cyclic heptapeptide designed as an analogue of alpha-melanocyte-stimulating hormone, the naturally occurring peptide involved in pigmentation signalling. Its sequence is conventionally written as Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, with a lactam bridge joining the aspartate side chain to the lysine side chain. The empirical formula is C50H69N15O9 and the monoisotopic mass lies near 1023.5 daltons. N-terminal acetylation and the D-configured phenylalanine both increase resistance to enzymatic breakdown compared with the parent hormone.

Pharmacologically, melanotan-2 behaves as a non-selective agonist across the melanocortin receptor family. Binding at MC1R on dermal melanocytes promotes eumelanin synthesis, which underlies the tanning response described in early human work. Activity at the centrally expressed MC4R receptor is associated with reported effects on appetite and erectile function. Because the peptide does not discriminate strongly among receptor subtypes, attributing any single observed effect to one receptor pathway is generally not possible without selective antagonists or receptor knockout models.

Melanotan-2 at a glance

PropertyValueNotes
Molecular formulaC50H69N15O9Free base; salt forms add to total mass
Molecular massAbout 1024 daltonsCalculated for the free base
Structural classCyclic heptapeptideContains D-phenylalanine and norleucine
Parent hormoneAlpha-melanocyte-stimulating hormoneEndogenous tridecapeptide of 13 residues
Receptor profileNon-selective melanocortin agonistInteracts with MC1R, MC3R, MC4R and MC5R

Identity and Chemical Background

Melanotan-2 is a synthetic linear peptide built from seven amino acids arranged in a short chain. Its sequence is commonly written as Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-NH2, which includes a modified N-terminus and an amidated C-terminus. The molecule belongs to the melanocortin family and acts as a receptor agonist. Structural features such as the D-phenylalanine residue and the Nle substitution are associated with increased stability against enzymatic degradation relative to the natural parent peptide.

The compound emerged from research programs in the 1980s that examined analogues of alpha-melanocyte-stimulating hormone for pigmentation and photoprotection. Investigators modified the native sequence to extend activity duration and potency. A related analogue, afamelanotide, was developed within the same broad line of inquiry and eventually gained approval in certain jurisdictions for a rare light-sensitivity condition. Melanotan-2 itself did not progress through the same regulatory route and has no approved therapeutic indication.

Related pages on this site

Background from the literature

==== Monoubiquitylation ==== Monoubiquitylation is the addition of one ubiquitin molecule to one substrate protein residue. Multi-monoubiquitylation is the addition of one ubiquitin molecule to multiple substrate residues. The monoubiquitylation of a protein can have different effects to the polyubiquitylation of the same protein. The addition of a single ubiquitin molecule is thought to be required prior to the formation of polyubiquitin chains. Monoubiquitylation affects cellular processes such as membrane trafficking, endocytosis and viral budding.

=== Marsupials, monotremes and bats === The shape of the glans varies among different marsupial species. In most marsupials, the glans is divided, but male macropods have an undivided glans penis. The glans penis is also divided into two parts in platypuses and echidnas. Males of Racey's pipistrelle bat have a narrow, egg-shaped glans penis.

== Media == The Cherokee Nation publishes the Cherokee Phoenix, currently a monthly newspaper. The paper has operated nearly continuously since 1828, publishing editions in both English and the Cherokee syllabary (also known as the Sequoyah syllabary). It holds historical significance as both the first newspaper to be published by Native Americans in the United States and the first to be published in a Native American language.

Sources: en.wikipedia.org

Reference notes

== Production == BASF's recent success is characterized by a focus on creating resource efficient product lines after completely abandoning consumer products. This strategy was reflected in production by a re-focus towards integrated production sites. The largest such integrated production site is located in Ludwigshafen employing 33,000 people. Integrated production sites are characterized by co-location of many individual production lines (producing a specific chemical), which share an interconnected material flow. Piping is used ubiquitously for volume materials. All production lines use common raw material sourcing and feed back waste resources, which can be used elsewhere (e.g. steam of various temperatures, sulfuric acid, carbon monoxide). The economic incentive for this approach is high resource and energy efficiency of the overall process, reduced shipping cost and associated reduced risk of accidents. Due to the high cost of such an integrated production site, it establishes a high entry barrier for competitors trying to enter the market for volume chemicals. BASF built a new chemical complex in Dahej, Gujarat at a cost of $100 million. This facility has South Asia's first methylene diphenyl diisocyanate (MDI) splitter for processing crude MDI. BASF has 8 production facilities in India. BASF SE has succeeded in developing a semi-crystalline polyamide that allows light to pass through largely unhindered, known as Ultramid.

=== Surgical removal === Epididymotomy is the placement of an incision into the epididymis and is sometimes considered a treatment option for acute suppurating epididymitis. Epididymectomy is the surgical removal of the epididymis, sometimes performed for post-vasectomy pain syndrome and for refractory cases of epididymitis. Epididymectomy is also performed for sterilization on some male animals of livestock species so they can be used to detect estrus in females ready for artificial insemination.

==== Renal cell carcinoma ==== The VHL (Von Hippel–Lindau) gene encodes a component of an E3 ubiquitin ligase. VHL complex targets a member of the hypoxia-inducible transcription factor family (HIF) for degradation by interacting with the oxygen-dependent destruction domain under normoxic conditions. HIF activates downstream targets such as the vascular endothelial growth factor (VEGF), promoting angiogenesis. Mutations in VHL prevent degradation of HIF and thus lead to the formation of hypervascular lesions and renal tumors.

Sources: en.wikipedia.org

Notes from published material

Surgical technique – the septal mucosal flap The surgeon cuts the anteriorly based septal mucosal tissue-flap as widely as possible, and then releases it with a low, posterior back-cut; but only as required to allow the rotation of the tissue-flap into the nasal wound.

The three substrates of this enzyme are (E)-coniferyl aldehyde, oxidised nicotinamide adenine dinucleotide (NAD+), and water. Its products are ferulic acid, reduced NADH, and a proton. The enzyme can use nicotinamide adenine dinucleotide phosphate as an alternative cofactor. This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is coniferyl aldehyde:NAD(P)+ oxidoreductase.

==== The Congress of Vienna ==== After Napoleon's defeat, a new European order was established at the Congress of Vienna, which met in the years 1814 and 1815. Adam Jerzy Czartoryski, a former close associate of Emperor Alexander I, became the leading advocate for the Polish national cause. The Congress implemented a new partition scheme, which took into account some of the gains realized by the Poles during the Napoleonic period. The Duchy of Warsaw was replaced in 1815 with a new Kingdom of Poland, unofficially known as Congress Poland. The residual Polish kingdom was joined to the Russian Empire in a personal union under the Russian tsar and it was allowed its own constitution and military. East of the kingdom, large areas of the former Polish–Lithuanian Commonwealth remained directly incorporated into the Russian Empire as the Western Krai. These territories, along with Congress Poland, are generally considered to form the Russian Partition. The Russian, Prussian, and Austrian "partitions" are informal names for the lands of the former Commonwealth, not actual units of administrative division of Polish–Lithuanian territories after partitions. The Prussian Partition included a portion separated as the Grand Duchy of Posen. Peasants under the Prussian administration were gradually enfranchised under the reforms of 1811 and 1823. The limited legal reforms in the Austrian Partition were overshadowed by its rural poverty. The Free City of Cracow was a tiny republic created by the Congress of Vienna under the joint supervision of the three partitioning powers.

Sources: en.wikipedia.org

Frequently asked questions

Is melanotan-2 approved for medical use?

No regulatory agency has authorised melanotan-2 as a medicine for any indication. It circulates mainly as a research chemical or through unregulated channels. As a result, identity, purity and content are not independently guaranteed.

How does melanotan-2 differ from melanotan-1?

Melanotan-1, also called afamelanotide, is a linear analogue with greater selectivity for MC1R and has received approval in some jurisdictions for a specific photosensitivity disorder. Melanotan-2 is cyclic, less selective, and reaches central receptors more readily. The two are often confused in online discussion despite different pharmacology and regulatory status.

What is the connection to alpha-MSH?

Alpha-MSH is an endogenous tridecapeptide derived from pro-opiomelanocortin. Melanotan-2 reproduces its core receptor-binding sequence inside a shortened, stabilised ring. The result is a molecule with a longer effective half-life and higher potency than the parent hormone.

What is melanotan-2 chemically?

It is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone, containing seven amino acids with a lactam ring and a D-configured phenylalanine residue. It is supplied as a lyophilised powder for laboratory research.

Network