en · de · es · fr · pt
compound-index.peptides9002.com › Data › Melanotan-2 Structure And Receptor Pharmacology — Reference Sheet

Melanotan-2 Structure And Receptor Pharmacology — Reference Sheet

By Editorial Desk · published 2026-06-03 · last reviewed 2026-06-18 · Data

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

This page was last updated on 2026-06-18 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.

No regulatory authority has approved melanotan-2 for human use, and several countries classify it as a prescription-only or controlled substance, which restricts lawful supply. Material sold online is generally labelled as a research chemical and is not required to meet pharmaceutical standards of identity or purity. Published human data consist mainly of small uncontrolled studies, case reports and adverse-event notifications, so the evidence base is descriptive rather than confirmatory. Whether repeated melanocyte stimulation alters long-term naevus behaviour remains an open question that no completed trial has resolved.

Background and Receptor Mechanism

Melanotan II is a synthetic cyclic heptapeptide analog derived from the core sequence of alpha-melanocyte-stimulating hormone. Researchers at the University of Arizona synthesized it during the 1980s while studying pigmentation and appetite signaling. The compound is not an approved medicine in any major jurisdiction and appears mainly in laboratory and research-chemical settings. Its structure incorporates a lactam bridge between side chains, which constrains the ring and slows enzymatic breakdown relative to the natural hormone.

Melanotan II binds several melanocortin receptor subtypes rather than a single target. MC1R on melanocytes drives melanin synthesis, while MC3R and MC4R participate in energy balance, appetite, and sexual response pathways. This lack of selectivity explains why reported effects extend beyond skin darkening. Substitutions at positions four and seven, including norleucine and D-phenylalanine, increase potency and resistance to peptidases. Understanding which receptor mediates which effect remains an active area of investigation.

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

Background and Mechanism of Melanotan-2

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.

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.

Related pages on this site

Melanotan II Background and Mechanism

Melanotan II is a synthetic cyclic heptapeptide that acts as an agonist at melanocortin receptors. It was designed as a structural analogue of alpha-melanocyte-stimulating hormone, the endogenous peptide involved in pigment production. The analogue carries a lactam bridge that constrains the ring and slows enzymatic breakdown relative to the native hormone. In research literature it appears under several abbreviations, and naming conventions are not fully standardized. Published descriptions usually place it within the broader melanocortin agonist family.

Receptor binding at MC1R on melanocytes raises intracellular cyclic AMP and increases expression of tyrosinase and related enzymes. The downstream result is greater synthesis of eumelanin, the dark pigment, without ultraviolet exposure acting as the trigger. The compound is not selective, however, and also engages MC3R, MC4R and MC5R, which are expressed in the central nervous system and elsewhere. That lack of selectivity is the explanation usually offered for effects reported outside pigmentation, including appetite suppression and nausea. Selectivity remains a central theme in comparative studies of related peptides.

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.

Notes from published material

Machaca – a dish prepared most commonly from dried, spiced beef or pork, then rehydrated and pounded to make it tender. The reconstituted meat would then be used to prepare any number of dishes. Meat extract – highly concentrated meat stock, usually made from beef. It is used to add meat flavor in cooking, and to make broth for drinking. Meat extracts have largely been supplanted by bouillon cubes and yeast extract.

Similarly, China permits nationals of non—visa-exempt ASEAN countries to visit Guilin without a visa for a maximum of 6 days if they travel with an approved tour group and enter China from Guilin Liangjiang International Airport. They may not visit other cities within Guangxi or other parts of mainland China. Neither the People's Republic of China nor the Republic of China recognises the passports issued by the other, and neither considers travel between mainland China and areas controlled by the Republic of China as formal international travel. There are arrangements in place for travel between territories controlled by the Republic of China and territories controlled by the People's Republic of China. More generally, authorities in mainland China maintain a system of residency registration known as hukou (Chinese: 户口; lit. 'household individual'), by which government permission is needed to change one's place of residence formally. It is enforced using identity cards. This system of internal border control measures effectively limited internal migration before the 1980s, but subsequent market reforms caused it to collapse as a means of migration control. An estimated 150 to 200 million people are part of the "blind flow" and have unofficially migrated, generally from poor rural areas to wealthy urban areas. However, unofficial residents are often denied official services such as education and medical care and are sometimes subject to both social and political discrimination.

Dilution of indoor pollutants with outdoor air is effective to the extent that outdoor air is free of harmful pollutants. Ozone in outdoor air occurs indoors at reduced concentrations because ozone is highly reactive with many chemicals found indoors. The products of the reactions between ozone and many common indoor pollutants include organic compounds that may be more odorous, irritating, or toxic than those from which they are formed. These products of ozone chemistry include formaldehyde, higher molecular weight aldehydes, acidic aerosols, and fine and ultrafine particles, among others. The higher the outdoor ventilation rate, the higher the indoor ozone concentration and the more likely the reactions will occur, but even at low levels, the reactions will take place. This suggests that ozone should be removed from ventilation air, especially in areas where outdoor ozone levels are frequently high.

Sources: en.wikipedia.org

Background from the literature

== Production and effects == Artificial production methods of radionuclides include neutron sources such as nuclear reactors, as well as particle accelerators such as cyclotrons. The radiation from radionuclides generally has a harmful effect on organisms including humans, although low levels of exposure occur naturally. The degree of harm depends on the nature and extent of the radiation (alpha, beta, gamma, or neutron), the amount and nature of exposure (close contact, inhalation or ingestion), and the element's biochemical properties (toxicity). Increased risk of cancer is unavoidable, and worse cases induce cancer, chronic radiation syndrome or acute radiation syndrome. Radionuclides can be used as weapons by the fallout effects of nuclear weapons and by radiological weapons. Radionuclides are used in nuclear medicine for both diagnosis and treatment. The term “theranostics” (or “theragnostics”) refers to the combination of diagnosis and therapy of a disease within a single medical procedure or technique. An imaging tracer made with radionuclides is a radioactive tracer. Radionuclide therapy is a form of radiotherapy. A pharmaceutical drug made with radionuclides is called a radiopharmaceutical.

== Genetics == The gene for G-CSF is located on chromosome 17, locus q11.2-q12. Nagata et al. found that the GCSF gene has four introns, and that two different polypeptides are synthesized from the same gene by differential splicing of mRNA. The two polypeptides differ by the presence or absence of three amino acids. Expression studies indicate that both have authentic GCSF activity. It is thought that stability of the G-CSF mRNA is regulated by an RNA element called the G-CSF factor stem-loop destabilising element.

The four-engined Fw 200 airliner flew nonstop between Berlin and New York City on 10 August 1938, making the journey in 24 hours and 56 minutes. It was the first aircraft to fly that route without stopping. The return trip on 13 August 1938, took 19 hours and 47 minutes. These flights are commemorated with a plaque in the Böttcherstraße street of Bremen. The Fw 190 Würger (Shrike/butcher-bird), designed from 1938 on, and produced in quantity from early 1941–1945, was a mainstay single-seat fighter for the Luftwaffe during World War II.

Sources: en.wikipedia.org

Further detail

By the early modern period, Neo-Latin had become the lingua franca of science, medicine, legal discourse, theology, and education in Europe. Over time, the use of Latin continued where international communication with specialist audiences was paramount. Later, where some of the discourse moved to French, English or German, translations into Latin would allow texts to cross language boundaries, while authors in countries with much smaller language populations or less known languages would tend to continue to compose in Latin. Latin's dominance over medicine began to change in the late seventeenth century, as philosophers and others began to write in their native language first, afterwards translating into Latin for international audiences. In the early part of the 1700s, Latin was still making a significant contribution to academic publishing, but was no longer dominant. Examples of modern medical dictionaries include Mosby's Dictionary of Medicine, Nursing & Health Professions, Stedman's, Taber's, and Dorland's.

==== TOC ==== Total organic carbon is measured by oxidizing organic molecules in the water to CO2 and measuring the increase in the CO2 concentration in the water after the oxidation. This change in carbon dioxide, or delta CO2, is used to determine concentration of organic carbon.

== Function == Members of the ADAM family are cell surface proteins with a unique structure, possessing both potential adhesion and protease domains. Sheddase, a generic name for the ADAM metallopeptidase, functions primarily to cleave membrane proteins at the cellular surface. Once cleaved, the sheddases release soluble ectodomains with an altered location and function. Although a single sheddase may "shed" a variety of substances, multiple sheddases can cleave the same substrate resulting in different consequences. This gene encodes an ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. ADAM10 (EC#: 3.4.24.81) is a sheddase, and has a broad specificity for peptide hydrolysis reactions. ADAM10 cleaves ephrin, within the ephrin/eph complex, formed between two cell surfaces. When ephrin is freed from the opposing cell, the entire ephrin/eph complex is endocytosed. This shedding in trans had not been previously shown, but may well be involved in other shedding events. In neurons, ADAM10 is the most important enzyme, with α-secretase activity for proteolytic processing of the amyloid precursor protein. ADAM10, along with ADAM17, cleaves the ectodomain of the triggering receptor expressed on myeloid cells 2 (TREM2), to produce soluble TREM2 (sTREM2), which has been proposed as a CSF and sera biomarker of neurodegeneration. ADAM10 belongs to subfamily A, the most ancestral subfamily of ADAM proteins, which is shared by all major groups of animals, choanoflagellates, fungi, and green algae from the class Mamiellophyceae.

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.

Is melanotan II an approved medication?

No regulator in a major market has approved it for human use. It appears in research settings and in products marketed outside pharmacy channels. Legal status for personal possession varies by country.

Network