cyclic heptapeptide comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Updated 2025-12-01. Numbers and descriptions here follow the published literature rather than marketing material.
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.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C50H69N15O9 | Cyclic heptapeptide, C-terminally amidated |
| Approximate molecular mass | 1024 Da | Monoisotopic mass of the free peptide |
| Appearance | White to off-white powder | Typically supplied as a lyophilised solid |
| Solubility class | Soluble in water and polar solvents | Also dissolves in neutral aqueous buffer |
| Common synonyms | Melanotan II, MT-II, MT-2 | Described as a melanocortin agonist in early literature |
Melanocytes are the pigment-producing cells of the skin, and they carry melanocortin-1 receptors on their surface. When the receptor is activated, cyclic adenosine monophosphate rises inside the cell and raises the activity of enzymes such as tyrosinase, which increases melanin output. Melanotan-2 binds melanocortin-1 receptors in vitro and in animal models, and this binding is generally described as the basis for the tanning effect. Other receptors account for different effects: melanocortin-4 receptors contribute to appetite and erectile signalling, while melanocortin-3 and melanocortin-5 receptors contribute to energy balance and exocrine function.
Early published reports described melanotan-2 as a tanning agent without sun protection, which means darkening is not the same as protection against ultraviolet radiation. Later studies explored the peptide in erectile dysfunction, hemorrhagic shock, and some skin conditions. No regulator in the United States or Europe has approved it for clinical use. Many products labelled melanotan-2 are sold without approval and their identity and purity are unverified. Its long-term safety in humans remains an open question.
Melanotan-2, also written Melanotan II, is a synthetic cyclic heptapeptide designed as an analogue of alpha-melanocyte-stimulating hormone. Its sequence is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, and the lactam bridge between the aspartate and lysine side chains constrains the peptide into a ring. This structural change increases receptor affinity and metabolic stability relative to the native hormone. The compound was created in the 1980s as a research tool for studying pigmentation biology.
== External links == NLM Hazardous Substances Databank – Plutonium, Radioactive Table of nuclides with 239Pu data at Kaye and Laby Online Half-life of Plutonium-239 Archived 2011-08-15 at the Wayback Machine
== History == The company was founded by Jerry Cole and John Parmer in 1955 and took up shop in a 1,200-square-foot (110 m2) loft on West Illinois Street in downtown Chicago. In the 1960s, Cole-Parmer acquired Masterflex peristaltic pumps, followed shortly by the purchases of Gilmont Instruments and Manostat Pumps. They were acquired by Fisher Scientific, now Thermo-Fisher Scientific, in 2001. On July 17, 2014, Thermo Fisher Scientific Inc. agreed to sell one of its lab units, Cole-Parmer, to private-equity firm GTCR for $480 million in cash. The company has previously said its $13.6 billion acquisition of Life Technologies Corp. would allow it to cut costs while gaining from next-generation genetic-sequencing machines. It has also sought to expand in Asia-Pacific markets. In 2025, Cole-Parmer was sold to Brookfield Asset Management Ltd.'s private equity group and Caisse de dépôt et placement du Québec for a reported 1.4 billion dollars (USD).
It also has the largest Brazilian community in the UK; one of the largest Indian communities; a significant Afro-Caribbean community; and more recent Romanian, Polish and Somali communities. The 2021 census showed that 1.3% of adults in Brent identified as transgender, derived from the Census question, "Is the gender you identify with the same as your sex registered at birth?". This gave Brent the second highest proportion of transgender adults after the Borough of Newham (at 1.5%). The overall proportion in England and Wales was 0.5% with Brighton, an area well known for its LGBT communities, 1%. However, Prof Michael Biggs of Oxford University showed there was a correlation between the proportion of transgender people in these areas and the proportion for whom English was not their first language (34% in Brent and 35% in Newham, compared to 9% nationally), suggesting the question was not fully understood by some. Prof Biggs described the figures as "irredeemably flawed". In September 2024, Mary Gregory, a deputy director at the ONS said some people may have misunderstood the question, saying there was "potential bias" in how the question was answered "by those who responded that they had lower levels of English proficiency, some of whom may have mistakenly given an answer suggesting they were trans". As a result, the ONS downgraded the data from "accredited official statistics" to "official statistics in development" to reflect the possible flaws.
NQ01 metabolizes benzoquinone toward polyphenols (counteracting the effect of MPO). GSH is involved with the formation of phenylmercapturic acid. Genetic polymorphisms in these enzymes may induce loss of function or gain of function. For example, mutations in CYP2E1 increase activity and result in increased generation of toxic metabolites. NQ01 mutations result in loss of function and may result in decreased detoxification. Myeloperoxidase mutations result in loss of function and may result in decreased generation of toxic metabolites. GSH mutations or deletions result in loss of function and result in decreased detoxification. These genes may be targets for genetic screening for susceptibility to benzene toxicity.
Nicotinamide riboside (NR) is utilized through an additional pathway involving phosphorylation by the nicotinamide riboside kinase enzymes (NRK1 and NRK2). In yeasts, NR has also been shown to be degraded by the nucleosidases Pnp1, Urh1 and Meu1, before being converted to NAD via the Preiss-Handler pathway and the action of the nicotinamidase Pnc1.
Sources: en.wikipedia.org
=== Functional analogues and derivatives === 3,3-Difluoroalanine: Difluorinated alanine with similar residue hydrophobicity to that of isoleucine. 3,3,3-Trifluoroalanine: Trifluorinated alanine that expresses properties of a suicide inhibitor for alanine racemases. 3,3,3-Trifluoroalanine N-carboxyanhydride: A cyclic anhydride of trifluorinated alanine investigated for use as a monomer in homo- and co-polymerisations.
The report published by the committee noted that while methadone itself was potentially addictive, it produced "considerably" less euphoria, sedation, and respiratory depression than morphine at equianalgesic doses and was thus interesting as a commercial drug. The same report also compared methadone to pethidine. German researchers reported that methadone was capable of producing strong morphine-like physical dependence, which is characterized by opioid withdrawal symptoms which are lesser in severity and intensity compared to morphine, but methadone was associated with a considerably prolonged or protracted withdrawal syndrome when compared to morphine. Morphine produced higher rates of self-administration and reinforcing behaviour in both human and animal subjects when compared to both methadone and pethidine. In comparison to equianalgesic doses of pethidine (Demerol), methadone was shown to produce less euphoria, but higher rates of constipation, and roughly equal levels of respiratory depression and sedation. In the early 1950s, methadone (most times the racemic HCl salts mixture) was also investigated for use as an antitussive. Isomethadone, noracymethadol, LAAM, and normethadone were first developed in Germany, the United Kingdom, Belgium, Austria, Canada, and the United States in the thirty or so years after the 1937 discovery of pethidine, the first synthetic opioid used in medicine.
Lots of work is currently being done to develop food and packaging solutions suitable for long duration space missions (2.5 y+). The primary goal is to provide palatable and nutritious food for astronauts, with the additional consideration of minimising volume, mass and waste. A key consideration is minimising the waste produced during long duration missions. The importance of biodegradable, edible and reusable packaging solutions have been emphasised, as these will reduce the strain on the solid-waste management system. Maximising the shelf life of foods has also been proposed, further helping to reduce waste. Research is also being conducted on food systems for lunar and planetary surface missions. A large focus is currently on crop processing, with the aim that crops grown hydroponically will constitute the majority of the menu. Initial crop ideas include white and sweet potatoes, soybeans, wheat and rice. A secondary benefit is the facilitating of production and regulation of oxygen and carbon dioxide. A focus is being placed on ensuring astronauts receive not only the recommended levels of nutrients to support mental and physical health, but the correct amounts required for long duration spaceflight. Research has shown that nutritional requirements change with the amount of time spent in space. For example, the recommended amount of calcium is 1000 mg/day, rising to 1200 mg/day in long duration missions.
==== Constitutive trafficking and changes in subunit composition ==== AMPA receptors are continuously being trafficked (endocytosed, recycled, and reinserted) into and out of the plasma membrane. Recycling endosomes within the dendritic spine contain pools of AMPA receptors for such synaptic reinsertion. Two distinct pathways exist for the trafficking of AMPA receptors: a regulated pathway and a constitutive pathway. In the regulated pathway, GluA1-containing AMPA receptors are trafficked to the synapse in an activity-dependent manner, stimulated by NMDA receptor activation. Under basal conditions, the regulated pathway is essentially inactive, being transiently activated only upon the induction of long-term potentiation. This pathway is responsible for synaptic strengthening and the initial formation of new memories. In the constitutive pathway, GluA1-lacking AMPA receptors, usually GluR2-GluR3 heteromeric receptors, replace the GluA1-containing receptors in a one-for-one, activity-independent manner, preserving the total number of AMPA receptors in the synapse. This pathway is responsible for the maintenance of new memories, sustaining the transient changes resulting from the regulated pathway. Under basal conditions, this pathway is routinely active, as it is necessary also for the replacement of damaged receptors. The GluA1 and GluA4 subunits consist of a long carboxy (C)-tail, whereas the GluA2 and GluA3 subunits consist of a short carboxy-tail.
Sources: en.wikipedia.org
No. It is a synthetic analogue carrying four amino acid changes, a lactam ring and an amidated C-terminus. The natural hormone is a linear thirteen-amino-acid peptide processed from proopiomelanocortin.
Afamelanotide is the linear analogue [Nle4-D-Phe7]-alpha-MSH, sometimes called melanotan I, while melanotan II is cyclic and carries three further substitutions. The two are distinct molecules and are not interchangeable in analytical testing.
Binding to the four melanocortin receptor subtypes is well documented in vitro. The relative contribution of each subtype to whole-body effects in humans is far less certain.
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.