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Melanotan-2 Identity And Receptor Pharmacology — Quick Reference

By Editorial Desk · published 2026-03-28 · last reviewed 2026-05-18 · Info

cyclic heptapeptide raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.

This page was last updated on 2026-05-18 and is reviewed periodically as new material appears.

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.

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.

Origins and Research Status

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.

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

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 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.

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Chemistry and Receptor Pharmacology

Published pharmacokinetic information is limited and comes mainly from small studies rather than registrational trials. Plasma half-life is usually described as short, on the order of tens of minutes, followed by rapid tissue distribution and clearance of the intact peptide. Metabolites and low concentrations of parent compound have been reported in urine, a detail relevant to anti-doping and forensic testing. Whether repeated exposure changes receptor sensitivity or clearance over time remains an open question. Values differ noticeably between analytical assays, so published numbers should be read as approximate rather than definitive.

Melanotan II is a synthetic cyclic heptapeptide with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, corresponding to a molecular formula of C50H69N15O9 and a monoisotopic mass near 1024 daltons. It was designed as a structural analogue of alpha-melanocyte-stimulating hormone, a peptide hormone produced by cleavage of proopiomelanocortin. A lactam bridge between the aspartate and lysine side chains closes the ring, and the C-terminal amide removes a free carboxyl group. Both modifications increase resistance to enzymatic degradation compared with the linear parent hormone. Four substitutions distinguish it from afamelanotide, the linear analogue studied under the name melanotan I.

Further detail

gene product Any of the biochemical material resulting from the expression of a gene, most commonly interpreted as the functional mRNA transcript produced by transcription of the gene or the fully constructed protein produced by translation of the transcript, though non-coding RNA molecules such as transfer RNAs may also be considered gene products. A measurement of the quantity of a given gene product that is detectable in a cell or tissue is sometimes used to infer how active the corresponding gene is.

Sidney Walter Fox (24 March 1912 – 10 August 1998) was a Los Angeles-born biochemist responsible for discoveries on the origins of biological systems. Fox explored the synthesis of amino acids from inorganic molecules, the synthesis of proteinous amino acids and amino acid polymers called "proteinoids" from inorganic molecules and thermal energy, and created what he thought was the world's first protocell out of proteinoids and water. He called these globules "microspheres". Fox believed in the process of abiogenesis where life spontaneously organized itself from the colloquially known "primordial soup;" poolings of various simple organic molecules that existed during the time before life on Earth. He also suggested that his experiments possessed conditions that were similar to those of primordial Earth. In his experiments, Fox demonstrated that it is possible to create protein-like structures from inorganic molecules and thermal energy. Fox went on to create microspheres that he said closely resembled bacterial cells and concluded that they could be similar to the earliest forms of life or protocells.

Unlike atomic absorption spectroscopy, which can only measure a single element at a time, ICP-MS has the capability to scan for all elements simultaneously. This allows rapid sample processing. A simultaneous ICP-MS that can record the entire analytical spectrum from lithium to uranium in every analysis won the Silver Award at the 2010 Pittcon Editors' Awards. An ICP-MS may use multiple scan modes, each one striking a different balance between speed and precision. Using the magnet alone to scan is slow due to hysteresis but is precise. Electrostatic plates can be used in addition to the magnet to increase the speed, and with multiple collectors can allow a scan of every element from Lithium 6 to Uranium Oxide 256 in less than a quarter of a second. For low detection limits, interfering species and high precision, the counting time can increase substantially. The rapid scanning, large dynamic range and large mass range of ICP-MS is ideally suited to measuring multiple unknown concentrations and isotope ratios in samples that have had minimal preparation (an advantage over TIMS). The analysis of seawater, urine, and digested whole rock samples are examples of industry applications. These properties also lend well to laser-ablated rock samples, where the scanning rate is fast enough to enable a real-time plot of any number of isotopes. This also allows easy spatial mapping of mineral grains.

=== Essendon: 2008-2012 === Prismall returned from injury towards the second half of the 2009 season for the Essendon Bombers and had an injury free return. He played 13 games for the club in 2009 and was a regular contributor, kicking five goals. In the 2010 season, Prismall was in and out of the Essendon team. His performances were not consistent and his ball skills were lacking. Towards the end of the season, however, his form improved considerably, despite the team's poor performances on the field. After a reconstruction on his right knee in 2008, he injured his left knee in the opening minutes of round 19, 2011 match against Collingwood and was out for the rest of the season. Prismall was delisted at the end of the 2012 season.

== Treatment == Treatment of tea and toast syndrome is centered primarily around resolving hyponatremia. Treatment choice depends on the type of hyponatremia. Traditional treatment for hyponatremia depends on the volume load in the person. For those who are euvolemic (normal body volume load), fluid intake should be restricted. In those that are hypovolemic (low body volume load), give isotonic saline. In those that are hypervolemic (high body volume load), diuresis should be induced. Elderly patients may present in any of these volume states. However, "tea and toast" syndrome patients typically present euvolemic hyponatremia since their hyponatremia is caused by low solute intake. These patients must receive proper nutrition that is higher in protein and electrolyte intake. The Health and Medicine Division of the National Academies of Science, Engineering, and Medicine recommends that older adults improve their diet by consuming more fish, low-fat dairy products, and whole grains (such as fortified breakfast cereals). Older adults can also improve their diet by snacking on nuts and legumes as well as ensuring that they include fruit and vegetables at the center of their diet.

Sources: en.wikipedia.org

Supporting material

Adenosine diphosphate ribose (ADPR) is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. ADPR is created from cyclic ADP-ribose (cADPR) by the CD38 enzyme using nicotinamide adenine dinucleotide (NAD+) as a cofactor. ADPR binds to and activates the TRPM2 ion channel. ADPR is the most potent agonist of the TRPM2 channel. cADPR also binds to TPRM2, and the action of both molecules is synergistic, with both molecules enhancing the action of the other molecule in activating the TRPM2 channel. Researchers are not sure how the Adenosine diphosphate reacts with the TRPM2 channel, but the ribose sugar may play a role in activating the TRPM2 ion channel. Researchers believe that co-targeting DNA-dependent protein kinase and poly(adenosine diphosphate-ribose) polymerase-1 does not promote apoptosis or mitotic catastrophe of cancer cells after radiation.

Among the military operations in which Poles held out the longest (until late September or early October) were the Siege of Warsaw, the Battle of Hel and the resistance of the Independent Operational Group Polesie. Warsaw fell on 27 September after a heavy German bombardment that killed tens of thousands civilians and soldiers. Poland was ultimately partitioned between Germany and the Soviet Union according to the terms of the German–Soviet Frontier Treaty signed by the two powers in Moscow on 29 September. Gerhard Weinberg has argued that the most significant Polish contribution to World War II was sharing its code-breaking results. This allowed the British to perform the cryptanalysis of the Enigma and decipher the main German military code, which gave the Allies a major advantage in the conflict. As regards actual military campaigns, some Polish historians have argued that simply resisting the initial invasion of Poland was the country's greatest contribution to the victory over Nazi Germany, despite its defeat. The Polish Army of nearly one million men significantly delayed the start of the Battle of France, planned by the Germans for 1939. When the Nazi offensive in the West did happen, the delay caused it to be less effective, a possibly crucial factor in the victory of the Battle of Britain. After Germany invaded the Soviet Union as part of its Operation Barbarossa in June 1941, the whole of pre-war Poland was overrun and occupied by German troops.

Instead, for centuries "Europe has (with only just sufficient intervals to enable the combatants to recruit their wasted energies) been one vast and continued battle-field…" He criticized Lord Bacon for his adherence to the balance of power as a universal rule:

mRNA vaccines offer specific advantages over traditional vaccines. Because mRNA vaccines are not constructed from an active pathogen (or even an inactivated pathogen), they are non-infectious. In contrast, traditional vaccines require the production of pathogens, which, if done at high volumes, could increase the risks of localized outbreaks of the virus at the production facility. Another biological advantage of mRNA vaccines is that since the antigens are produced inside the cell, they stimulate cellular immunity, as well as humoral immunity. mRNA vaccines have the production advantage that they can be designed swiftly. Moderna designed their mRNA-1273 vaccine for COVID-19 in 2 days. They can also be manufactured faster, more cheaply, and in a more standardized fashion (with fewer error rates in production), which can improve responsiveness to serious outbreaks. The Pfizer–BioNTech vaccine originally required 110 days to mass-produce (before Pfizer began to optimize the manufacturing process to only 60 days), which was substantially faster than traditional flu and polio vaccines. Within that larger timeframe, the actual production time is only about 22 days: two weeks for molecular cloning of DNA plasmids and purification of DNA, four days for DNA-to-RNA transcription and purification of mRNA, and four days to encapsulate mRNA in lipid nanoparticles followed by fill and finish. The majority of the days needed for each production run are allocated to rigorous quality control at each stage.

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 is melanotan II?

It is a synthetic cyclic peptide designed as an analog of alpha-melanocyte-stimulating hormone. It acts on melanocortin receptors and is best known from research into pigmentation. It is not an approved pharmaceutical product.

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