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Melanotan-2 Identity And Receptor Pharmacology — Reference Sheet

By Editorial Desk · published 2025-07-15 · last reviewed 2025-08-26 · Blog

MC1R is one of those subjects where the details matter more than the headlines. This page pulls together the background, the mechanisms, and the practical points readers ask about most.

Updated 2025-08-26. Numbers and descriptions here follow the published literature rather than marketing material.

Melanotan-2 Identity and Receptor Pharmacology

Research interest has centred on photoprotection and pigmentation, with a smaller body of work on appetite and sexual function. Published human data remain limited to small, frequently uncontrolled studies, and the compound has never received marketing approval from a national medicines regulator. Most laboratory work treats it as a pharmacological tool for probing melanocortin signalling in cell culture or animal models. Whether pigmentation changes observed in people translate into measurable protection against ultraviolet-induced DNA damage remains an open question.

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.

Chemical Background and Receptor Activity

Melanotan-2 is frequently confused with afamelanotide, a linear analogue authorised in the European Union for erythropoietic protoporphyria. The two compounds differ in chain length, ring structure and receptor selectivity, so findings for one cannot be transferred directly to the other. Published controlled human data on melanotan-2 remain sparse, and much of what circulates online derives from small studies or unpublished reports. Questions about effect size, dose-response behaviour and long-term safety therefore remain unresolved.

Melanotan-2 is a synthetic cyclic heptapeptide designed as an analogue of alpha-melanocyte-stimulating hormone. Its sequence incorporates a lactam bridge that constrains the peptide into a ring, which increases resistance to enzymatic breakdown relative to the natural hormone. Researchers at the University of Arizona synthesised the compound in the late 1980s and early 1990s while studying pigmentation pathways. It has never received marketing approval from any national medicines regulator. In the scientific literature it is usually described as a laboratory research reagent rather than a therapeutic product.

Melanotan-2 at a glance

PropertyValueNotes
Common synonymsMelanotan II; MT-II; N-acetyl-norleucyl-cyclo[Asp-His-D-Phe-Arg-Trp-Lys] amideNaming follows peptide convention; the numeral distinguishes it from melanotan-1
Molecular formulaC50H69N15O9Includes the lactam bridge; no counter-ion assumed
Monoisotopic mass1023.53 DaFree base; salts and counter-ions shift the observed value
AppearanceWhite to off-white lyophilised powderBatch-to-batch colour variation is not itself proof of impurity
Typical analytical methodRP-HPLC purity determination with ESI-MS identity confirmationRetention time alone does not establish sequence identity

Origins and Research Status

The compound was developed in the late 1980s and 1990s by academic researchers investigating photoprotection. The rationale held that stimulating melanin production might reduce ultraviolet damage to skin and lower skin cancer risk. Early work examined receptor binding, pigment response, and short-term tolerability in small studies. That program did not produce an approved drug, and formal development stalled after early-phase trials. Whether induced pigmentation confers meaningful photoprotection remains an open question.

Outside regulated medicine, melanotan II circulates through online vendors as a research chemical, often marketed for tanning. Products sold this way vary widely in purity, concentration, and labeling accuracy, and independent testing has documented discrepancies. Published reports describe both pigment effects and adverse reactions, including nausea, flushing, and darkening of existing moles. Long-term safety data are sparse, and no large controlled trial has established a risk profile. Questions about cumulative effects on melanocytes remain unresolved in the literature.

Melanotan II is a synthetic peptide analog modeled on alpha-melanocyte-stimulating hormone, a naturally occurring signaling peptide involved in pigmentation. Its structure is a cyclic heptapeptide containing two non-natural substitutions, norleucine at position four and D-phenylalanine at position seven. These modifications resist enzymatic breakdown and extend the molecule's activity relative to the native hormone. The compound binds melanocortin receptors and is studied mainly as a pharmacological tool rather than a therapeutic product. It has never received approval as a medicine in any major jurisdiction.

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Peptide Identity and Structural Background

Structurally, Melanotan-2 retains the core recognition motif of alpha-melanocyte-stimulating hormone while adding a lactam bridge that links two side chains and constrains the molecule into a ring. This modification lowers susceptibility to enzymatic degradation. The compound acts as an agonist at melanocortin receptors, particularly subtypes associated with melanin production. Because the same receptor family influences several physiological processes, researchers note that its activity is not confined to pigmentation alone. Receptor selectivity continues to be examined in published studies.

Melanotan-2 is a synthetic cyclic heptapeptide designed as an analogue of alpha-melanocyte-stimulating hormone, a naturally occurring peptide involved in pigmentation signalling. Its sequence incorporates modified residues that increase potency and extend biological activity relative to the native hormone. The compound binds receptors of the melanocortin family and is examined mainly in laboratory research. It does not occur naturally and exists only as a manufactured chemical entity produced by solid-phase synthesis.

Identity and Chemical Background

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.

Melanocortin receptors comprise five subtypes with distinct tissue distributions and functions. Melanotan-2 is described in the literature as a non-selective agonist that engages several of these subtypes, including MC1R, MC3R, MC4R, and MC5R. MC1R is the subtype most directly linked to melanin production in skin cells. Because the compound is not subtype-selective, its observed effects in experimental settings are generally attributed to activity across multiple receptor pathways rather than to a single target.

Melanotan-2 Identity And Regulatory Status

Melanotan II is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone, a naturally occurring peptide involved in pigmentation signalling. Its structure substitutes a lactam bridge between side chains to increase stability relative to the native hormone. The compound is also known by the shorthand MT-II and by several non-proprietary synonyms used in research catalogues. It is not an approved therapeutic product in any major jurisdiction; material sold under this name is typically offered as a laboratory reagent rather than as a medicine.

Activity is attributed to agonism at melanocortin receptors, particularly MC1R and MC4R. Activation of MC1R on melanocytes increases melanin synthesis, which underlies the reported tanning effect. MC4R engagement in the central nervous system is linked to appetite suppression and to effects on sexual arousal reported in early clinical studies. Those studies were small and were not designed to establish efficacy or long-term safety. Receptor selectivity among the melanocortin subtypes is not absolute, which complicates attribution of any effect to a single pathway.

Reference notes

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=== Medical use === Cryosurgery procedures such as cryoablation use liquid argon to destroy tissue such as cancer cells. It is used in a procedure called "argon-enhanced coagulation", a form of argon plasma beam electrosurgery. The procedure carries a risk of producing gas embolism and has resulted in the death of at least one patient. Blue argon lasers are used in surgery to weld arteries, destroy tumors, and correct eye defects. Argon has also been used experimentally to replace nitrogen in the breathing or decompression mix known as Argox, to speed the elimination of dissolved nitrogen from the blood.

The four-stage plan specifies roles and responsibilities of governments and industry partners. At this point, the country was at level two, dubbed "Keeping Australia moving", after going through a preparation and planning phase. The federal government announced the cutting of fuel excise by 50%, along with a three-month pause on road user charges for trucks. Singapore and Australia have signed an agreement to keep their energy trade flowing, with Singapore diversifying the origins of its supplies of crude oil.

Attempts to reunite the Polish lands gained momentum in the 13th century, and in 1295, Duke Przemysł II of Greater Poland managed to become the first ruler since Bolesław II to be crowned king of Poland. He ruled over a limited territory and was soon killed. In 1300–1305 King Wenceslaus II of Bohemia also reigned as king of Poland. The Piast Kingdom was effectively restored under Władysław I the Elbow-high (r. 1306–1333), who became king in 1320. In 1308, the Teutonic Knights seized Gdańsk and the surrounding region of Pomerelia. King Casimir III the Great (r. 1333–1370), Władysław's son and the last of the Piast rulers, strengthened and expanded the restored Kingdom of Poland, but the western provinces of Silesia (formally ceded by Casimir in 1339) and most of Polish Pomerania were lost to the Polish state for centuries to come. Progress was made in the recovery of the separately governed central province of Mazovia, however, and in 1340, the conquest of Red Ruthenia began, marking Poland's expansion to the east. The Congress of Kraków, a vast convocation of central, eastern, and northern European rulers probably assembled to plan an anti-Turkish crusade, took place in 1364, the same year that the future Jagiellonian University, one of the oldest European universities, was founded. On 9 October 1334, Casimir III confirmed the privileges granted to Jews in 1264 by Bolesław the Pious and allowed them to settle in Poland in great numbers.

== Chemistry == Epimedium wushanense contains a number of flavonoids. 37 compounds were characterized from the underground and aerial parts of the plant. Among them, 28 compounds were prenylflavonoids. The predominant flavonoid, epimedin C, ranged from 1.4 to 5.1% in aerial parts and 1.0 to 2.8% in underground parts.

Sources: en.wikipedia.org

Reference notes

== Society and culture == Modafinil's use varies by region. In the US, it is approved for adult narcolepsy, shift work sleep disorder, and obstructive sleep apnea, but not for children. In the UK and the EU, since 2014, it is approved solely for narcolepsy, including in children (pediatric narcolepsy), with its use for other conditions restricted by the European Medicines Agency. Modafinil is not approved for use by children in multiple jurisdictions.

Lactic acid fermentation is a metabolic process by which glucose or other six-carbon sugars (also, disaccharides of six-carbon sugars, e.g. sucrose or lactose) are converted into cellular energy and the metabolite lactate, which is lactic acid in solution. It is an anaerobic fermentation reaction that occurs in some bacteria and animal cells, such as muscle cells. It is also used extensively to preserve food and create novel flavours. Despite the name, milk is not required by this process. If oxygen is present in the cell, many organisms will bypass fermentation and undergo cellular respiration; however, facultative anaerobic organisms will both ferment and undergo respiration in the presence of oxygen. Sometimes even when oxygen is present and aerobic metabolism is happening in the mitochondria, if pyruvate is building up faster than it can be metabolized, the fermentation will happen anyway. Lactate dehydrogenase catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD+. In homolactic fermentation, one molecule of glucose is ultimately converted to two molecules of lactic acid. Heterolactic fermentation, by contrast, yields carbon dioxide and ethanol in addition to lactic acid, in a process called the phosphoketolase pathway.

An effective codrug should be pharmacologically inactive in its own right but should release the constituent drugs upon biochemical breakage of the chemical linkage at the target tissue where their therapeutic effects are needed. As such, the chemical linkage (usually a covalent bond) should be subjectable to biodegradation, such as hydrolysis, by an enzymatic or non-enzymatic mechanism. The differential distribution of enzymes capable of catalyzing the breakage of the chemical linkage in different tissues may be exploited to achieve tissue-specific metabolism of the codrug to release the constituent drugs.

The "Learn" section of HPA includes educational resources, including information regarding antibody-based applications and techniques, a histology dictionary and educational 3D videos. The dictionary is an interactive tool for free full-screen exploration of whole slide images of normal human organs and tissues, cancer tissues and cell structures, guided with detailed annotations of all major structural elements. Educational videos have been produced by HPA, depicting the exploration of the human body in 3D, using antibody-based profiling of tissues and light sheet microscopy. The movies are available at the HPA website as well as on a YouTube channel. Datasets used in HPA are made freely available to encourage further studies within the research community. Access to the extensive datasets is given through the downloadable data page of HPA, wherein 29 different downloadable files are available, containing genome‐wide data across various assays.

Sources: en.wikipedia.org

Frequently asked questions

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.

How does it differ from the natural hormone?

The natural hormone is a linear tridecapeptide that is rapidly degraded in circulation. Melanotan-2 is shortened, cyclised, N-terminally acetylated, and carries a D-amino acid substitution, all of which slow enzymatic breakdown.

Does it hold any regulatory approval?

No national medicines regulator has approved melanotan-2 for therapeutic or cosmetic use. In several jurisdictions it is treated as an unapproved prescription medicine, and its legal classification differs from country to country.

What class of compound is melanotan-2?

It is a synthetic cyclic heptapeptide modelled on alpha-melanocyte-stimulating hormone. A lactam bridge links two side chains, forming a ring that stabilises the molecule against proteolysis. It belongs to the broader melanocortin peptide family.

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