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Melanotan-2 Structure And Receptor Pharmacology — Background and Details

By Editorial Desk · published 2025-11-18 · last reviewed 2025-12-26 · Info

melanocortin receptor 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 2025-12-26 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.

Background and Chemical Profile

Melanotan-2 is a synthetic peptide designed as an analog of alpha-melanocyte-stimulating hormone, a signaling molecule produced in the pituitary and skin. Its structure is a linear chain of seven amino acids that folds into a ring through an internal lactam bridge joining two side chains. The compound is sometimes written as MT-II or MEL-2 in informal and commercial contexts. It belongs to the melanocortin peptide family, a group of short signaling molecules that share a conserved core sequence recognized by melanocortin receptors.

Two structural changes distinguish the synthetic peptide from the natural hormone. A norleucine residue replaces methionine at one position, and a D-configured phenylalanine replaces the natural L-form at another. Both substitutions slow enzymatic breakdown, which extends the molecule's persistence relative to the parent hormone. The lactam bridge further constrains the backbone into a stable conformation. These features are standard design strategies in peptide chemistry and are not unique to this compound; they appear across many research peptides built for improved stability.

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

Chemistry and Receptor Pharmacology

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.

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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.

Background from the literature

=== Research === During his long career at WSLH, Inhorn pursued many different lines of medical research and public health intervention. In 1960, WSLH was involved in a large community program to promote the new Pap smear test for detecting the early stages of cervical cancer. Inhorn devoted many hours to training personnel in family planning clinics on how to carefully make and screen the Pap smear, both of which are essential to its success. During this time, Inhorn also became active in the American Society of Cytopathology. He chaired its committees to develop best practices in laboratory operation, and he eventually became president of ASC, later receiving the Papanicolaou Award for his contributions to the field of cytopathology. In addition, by 1960, new techniques in the field of cytogenetics permitted the study of infants and children with congenital malformations. Inhorn provided the laboratory component that permitted pediatricians from the UW Medical Center to study a large number of affected children. In particular, Down syndrome had been identified as having three chromosome 21s, instead of two. The Cytogenetics Lab at WSLH identified another trisomy (trisomy 13), an important discovery contributing to the genomic revolution that followed.

The Bentley compounds are a class of semi-synthetic opioids that were first synthesized by K. W. Bentley by Diels-Alder reaction of thebaine with various dienophiles. The compounds are also known as thevinols, orvinols, or bridged oripavine derivatives, due to the characteristic 6,14-endo-ethano- or etheno-bridge and substitution at the 7α position. Buprenorphine and etorphine are perhaps the best known of the family, which was the first series of extremely potent μ-opioid agonists, with some compounds in the series having over many thousands of times the analgesic potency of morphine.

== Operations and technology == By 2015, Lineage's facility network was ranked the second-largest in the world by the International Association of Refrigerated Warehouses. With 111 facilities in 21 states, Lineage also ranked as the second largest temperature-controlled warehousing and logistics company in the United States. In September 2020, Lineage raised $1.6 billion in equity for technology and expansion. In March 2021, Lineage raised $1.9 billion in equity for global greenfield developments, facility expansions, M&A and research and development. In July 2021, Lineage partnered with 8VC logistics technology venture capital firm, to further invest in the transportation and logistics technology sector.

Sources: en.wikipedia.org

Further detail

Dehydrogenase enzymes transfer electrons from the substrate to an electron carrier; what carrier is used depends on the reaction taking place. Common electron acceptors used by this subclass are NAD+, FAD, and NADP+. Electron carriers are reduced in this process and considered oxidizers of the substrate. Electron carriers are coenzymes that are often referred to as "redox cofactors."

On 2 March 1864, the Russian authority, compelled by the uprising to compete for the loyalty of Polish peasants, officially published an enfranchisement decree in Congress Poland along the lines of an earlier land reform proclamation of the insurgents. The act created the conditions necessary for the development of the capitalist system on central Polish lands. At the time when most Poles realized the futility of armed resistance without external support, the various sections of Polish society were undergoing deep and far-reaching evolution in the areas of social, economic and cultural development.

Reposado may be rested in oak barrels or casks as large as 20,000 litres (5,280 US gallons), allowing for richer and more complex flavors. The preferred oak comes from the US, France, or Canada, and is usually white oak. Some companies char the wood to impart a smoky flavor or use barrels previously used with different kinds of alcohol (e.g. whiskey or wine). Some reposados can also be aged in new wood barrels to achieve the same woody flavor and smoothness, but in less time. Añejos are often rested in barrels previously used to rest reposados. The barrels cannot be more than 600 litres (160 US gal), and most are in the 200 litres (53 US gal) range. Many of the barrels used are from whiskey distilleries in the US or Canada, and Jack Daniel's barrels are especially popular. This treatment creates many of the aspects of the dark color and more complex flavors of the añejo tequila. After aging of at least one year, the añejo can be removed from the wood barrels and placed in stainless steel tanks to reduce the amount of evaporation that can occur in the barrels.

Sources: en.wikipedia.org

Supporting material

The suffix -thiol is added to the name of the alkane. This method is nearly identical to naming an alcohol and is used by the IUPAC, e.g. CH3SH would be methanethiol. The word mercaptan replaces alcohol in the name of the equivalent alcohol compound. Example: CH3SH would be methyl mercaptan, just as CH3OH is called methyl alcohol. The term sulfhydryl- or mercapto- is used as a prefix, e.g. mercaptopurine.

===== Behavioral treatments ===== A 2018 systematic review and network meta-analysis of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that combination therapy with both contingency management and community reinforcement approach had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate). Other treatment modalities examined in the analysis included monotherapy with contingency management or community reinforcement approach, cognitive behavioral therapy, 12-step programs, non-contingent reward-based therapies, psychodynamic therapy, and other combination therapies involving these. Additionally, research on the neurobiological effects of physical exercise suggests that daily aerobic exercise, especially endurance exercise (e.g., marathon running), prevents the development of drug addiction and is an effective adjunct therapy (i.e., a supplemental treatment) for amphetamine addiction. Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions. In particular, aerobic exercise decreases psychostimulant self-administration, reduces the reinstatement (i.e., relapse) of drug-seeking, and induces increased dopamine receptor D2 (DRD2) density in the striatum. This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density.

Pentachlorophenol in the Pesticide Properties DataBase (PPDB) Non-CCA Wood Preservatives: Guide to Selected Resources - National Pesticide Information Center Archived 2007-10-31 at the Wayback Machine EPA on pentachlorophenol atsdr.cdc.gov on pentachlorophenol CDC – NIOSH Pocket Guide to Chemical Hazards EPA study that used the fungus Phanerochaete chrysosporium to aid in bioremediation of pentachlorophenol in soil[link removed] EPA ReRegistration – www.regulations.gov -Search docket ID EPA-HQ-OPP-2014-0653.

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.

What is melanotan-2?

It is a synthetic seven-amino-acid peptide modeled on alpha-melanocyte-stimulating hormone. It carries two non-natural substitutions and a cyclic bridge that increase its stability relative to the natural hormone. It circulates as a research chemical and is not an approved medicine.

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