If you have been reading about melanocortin receptor and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-03-04. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
Receptor-binding studies classify melanotan II as a non-selective melanocortin agonist. It interacts with MC1R, MC3R, MC4R and MC5R, with reported affinities in the low nanomolar range and no strong subtype preference. Activation of MC1R on dermal melanocytes shifts pigment synthesis toward eumelanin, the dark polymer deposited in melanosomes and transferred to keratinocytes. Because the same peptide engages MC4R in the hypothalamus, it also appears in animal work on food intake and erectile response, which is why it is discussed in both pigment and metabolic research. Which receptor populations dominate after systemic exposure in humans is not fully established.
Regulatory treatment varies by country. In the United States, melanotan-2 is not approved for any indication, and products marketed for human use fall outside the approved drug framework. Some other jurisdictions have placed it under prescription controls or listed it as a prohibited or restricted substance. Online listings frequently describe the material as a research chemical, a category that does not carry the same manufacturing and labelling requirements as approved medicines.
Solid peptide material is generally stable when kept cold and dry. Common practice is storage at -20 degrees Celsius or lower, with desiccant and protection from light. Repeated freeze-thaw cycles and exposure to moisture are associated with degradation, aggregation, or loss of material. Once dissolved, stability depends on solvent, concentration, and temperature, and solutions are usually treated as short-lived unless stability data support longer periods. Handling notes typically emphasise minimising time at ambient temperature.
Identity and purity are assessed with chromatographic and mass spectrometric techniques. Reversed-phase high-performance liquid chromatography separates the target peptide from related impurities and degradation products, and the resulting retention time is compared against a reference standard. Mass spectrometry, often coupled to liquid chromatography, confirms molecular mass. Amino acid analysis or peptide mapping can provide additional sequence-level confirmation when required. Results are only as reliable as the reference materials used alongside them.
| 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 |
The peptide was developed during the 1980s by researchers investigating melanocortin signalling and skin pigmentation pathways. Early work focused on analogues of alpha-melanocyte-stimulating hormone that would resist enzymatic breakdown more effectively than the parent molecule. Melanotan-2 emerged from that programme as a shortened, cyclised variant. Reports describing its synthesis and receptor activity later appeared in the scientific literature. Commercial availability grew through unregulated channels rather than through pharmaceutical approval.
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.
Melanotan-2 appears on the World Anti-Doping Agency prohibited list within the peptide hormone class, and several national regulators treat it as an unapproved prescription substance. Some countries restrict importation or sale for personal use. Because the compound is widely traded as a research chemical, the practical legal picture differs between jurisdictions and shifts over time. Human safety data covering long periods are limited, and whether repeated pigmentation changes carry any lasting risk to melanocytes remains an open question.
Freeze-dried melanotan-2 is normally kept as a desiccated powder at minus twenty degrees Celsius or lower, shielded from light and moisture. Peptides of this size degrade through hydrolysis, oxidation and deamidation, and each pathway accelerates as temperature and water activity rise. Repeated freeze-thaw cycles promote aggregation and loss of material, so aliquoting a stock solution before freezing is standard laboratory practice. Once dissolved, the solution is markedly less stable than the powder. In laboratory work, solutions are generally refrigerated and used within days rather than kept for months.
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.
Reversed-phase high-performance liquid chromatography is the routine method for purity assessment. Peptides absorb near 214 nm because of the peptide bond, and a gradient of acetonitrile in water separates the intact peptide from deletion sequences, oxidised products, and earlier-eluting fragments at neutral pH. Electrospray ionisation mass spectrometry provides an orthogonal check: the measured mass must agree with the theoretical value. Amino acid analysis and peptide mapping confirm structure but are used less often. Reference standards remain scarce because the peptide is not described in any pharmacopoeia.
Regulatory treatment varies by country. In the United States the peptide is not approved as a medicine, and products offered for human use may be treated as unapproved new drugs; some states also restrict sale. Australia, the United Kingdom, and European Union member states apply comparable restrictions to unapproved peptide products. Border agencies have seized shipments labelled as research chemicals. Classification may change over time, and the legal position for personal importation is not clearly settled in most published guidance.
Lyophilised melanotan-2 is supplied as a solid, which is more stable than a solution. The material is hygroscopic, so weighing is done quickly, in low humidity, with the container kept sealed. Reconstitution usually uses water for injection or bacteriostatic water, added down the wall of the vial to limit foaming. A reconstituted solution is held at 2 to 8 °C and kept away from light. Repeated freezing and thawing of the same vial is avoided because ice crystal formation and concentration effects degrade the peptide.
== Intracrines in biology and development == Intracrines are essential regulators of cellular differentiation and development. The intracellular mode of action allows for highly localized and sustained control over developmental processes, particularly in stem cell differentiation, organogenesis, and tissue remodeling.
=== Antithyroid drugs === Thyrostatics (antithyroid drugs) are drugs that inhibit the production of thyroid hormones, such as carbimazole (used in the UK) and methimazole (used in the US, Germany, and Russia), and propylthiouracil. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase and, thus, the formation of tetraiodothyronine (T4). Propylthiouracil also works outside the thyroid gland, preventing the conversion of (mostly inactive) T4 to the active form T3. Because thyroid tissue usually contains a substantial reserve of thyroid hormone, thyrostatics can take weeks to become effective, and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results.
=== Hoechst stains === Hoechst is a bis-benzimidazole derivative compound that binds to the minor groove of DNA. Often used in fluorescence microscopy for DNA staining, Hoechst stains appear yellow when dissolved in aqueous solutions and emit blue light under UV excitation. There are two major types of Hoechst: Hoechst 33258 and Hoechst 33342. The two compounds are functionally similar, but with a little difference in structure. Hoechst 33258 contains a terminal hydroxyl group and is thus more soluble in aqueous solution, however this characteristics reduces its ability to penetrate the plasma membrane. Hoechst 33342 contains an ethyl substitution on the terminal hydroxyl group (i.e. an ethylether group) making it more hydrophobic for easier plasma membrane passage
Takaki's theory, while incorrectly focusing on macronutrients, was a step in the right direction that resulted in correct treatment. However, keen-eyed observers were able to easily rebut Takaki's theories with counterexamples, so nutritional theories remained heterodox science. In 1897, Christiaan Eijkman, a Dutch physician and pathologist, published his mid-1880s experiments showing that feeding unpolished rice (instead of the polished variety) to chickens helped to prevent beriberi. This was the first experiment to show that not a major chemical, but some minor nutrient, was the true cause of beriberi. The following year, Sir Frederick Hopkins postulated that some foods contained "accessory factors"—in addition to proteins, carbohydrates, fats, and salt—that were necessary for the functions of the human body. In 1901, Gerrit Grijns, a Dutch physician and assistant to Christiaan Eijkman in the Netherlands, correctly interpreted beriberi as a deficiency syndrome, and between 1910 and 1913, Edward Bright Vedder established that an extract of rice bran is a treatment for beriberi. In 1929, Eijkman and Hopkins were awarded the Nobel Prize for Physiology or Medicine for their discoveries. In 1935, Robert R. Williams isolated and cheaply synthesized thiamine from rice bran, based on discoveries he had made as a researcher in Manila's Bureau of Science in 1910. Williams assigned the patents to a fund that worked to promote thiamine-enriched rice in Asia, and in Bataan in particular.
=== Editors === Francis Pharcellus Church (1859), editorial writer for the New York Sun and author of Yes, Virginia, There is a Santa Claus Horatio Sheafe Krans (1894), author and editor Simeon Strunsky (1900), literary editor of the New York Evening Post and editorial writer for The New York Times Lester Markel (1914), edited "Review of the Week", a section of The New York Times, which won the Special Awards and Citations Pulitzer Prize in 1953 Daniel Longwell (1922), co-founder and managing editor of Life Theodore M. Bernstein (1924), assistant managing editor of The New York Times Herbert Solow (1924), editor of Fortune Groff Conklin (1927), science fiction anthologist Emanuel Freedman (1931), foreign editor of The New York Times James Wechsler (1935), editorial page editor of the New York Post David Perlman (1939), former science editor of the San Francisco Chronicle Lester Bernstein (1940), former editor-in-chief of Newsweek Werner Wiskari (1941), international news editor of The New York Times Lucien Carr (1946), editor for United Press International Byron Dobell (1947), editor of American Heritage, Esquire; mentor to journalists Tom Wolfe, David Halberstam, and Mario Puzo Charles Peters (1949), founder and former editor-in-chief of The Washington Monthly Ashbel Green (1950), senior editor and vice president of Alfred A. Knopf Emile Capouya (1951), literary editor of The Nation 1969–1981 Robert Gottlieb (1952), editor of The New Yorker and president of Alfred A.
Sources: en.wikipedia.org
=== California === In 2001, California enacted phlebotomy licensure following a public health outcry about an on-the-job trained phlebotomist that re-used needles. California has two levels of phlebotomy licensure:
These strongly electrophilic NAIs allow for reactions with a wide range of nitrogen nucleophiles, including hindered and electron-deficient amines. An added benefit of the use of NMI as the base, due to its low pKa(H2O) of 7, is that the epimerization of labile stereogenic centers is minimized. The reaction by-products have high water solubility, facilitating reaction workup and isolation.
== External links == Overview of all the structural information available in the PDB for UniProt: P39060 (Human Collagen alpha-1(XVIII) chain) at the PDBe-KB. Overview of all the structural information available in the PDB for UniProt: P39061 (Mouse Collagen alpha-1(XVIII) chain) at the PDBe-KB.
=== Repair of DNA mutation and apoptosis === The damage to DNA due to exposure to UV rays will lead to the expression of p53, thereby leading to the eventual arrest of the cell cycle. This allows DNA repair mediated by endogenous mechanisms like the nucleotide excision repair system. In addition, apoptosis occurs if the damage is too severe. However, the apoptotic mechanisms decline with age, and if neither DNA repair mechanism nor apoptosis occurs, cutaneous tumorigenesis may result.
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.
Laboratory confirmation typically combines retention time matching on a chromatographic system with mass measurement. A reference standard of known identity is needed for a meaningful comparison. Sequence-level techniques can add further confirmation.