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Melanotan-2 Structure And Receptor Pharmacology — Reference Sheet

By Editorial Desk · published 2026-03-11 · last reviewed 2026-04-08 · Blog

If you have been reading about cyclic heptapeptide 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.

Updated 2026-04-08. Numbers and descriptions here follow the published literature rather than marketing material.

Melanotan-2 Structure and Receptor Pharmacology

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.

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.

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 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

Identity and Chemical Background

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.

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.

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Supporting material

Heart failure characteristically involves increased catecholamine activity on the heart, which is responsible for several deleterious effects, including increased oxygen demand, propagation of inflammatory mediators, and abnormal cardiac tissue remodeling, all of which decrease the efficiency of cardiac contraction and contribute to the low ejection fraction. Beta blockers counter this inappropriately high sympathetic activity, eventually leading to an improved ejection fraction, despite an initial reduction in ejection fraction. Trials have shown beta blockers reduce the absolute risk of death by 4.5% over a 13-month period. In addition to reducing the risk of mortality, the numbers of hospital visits and hospitalizations were also reduced in the trials. A 2020 Cochrane review found minimal evidence to support the use of beta blockers in congestive heart failure in children, however did identify that from the data available, that they may be of benefit. Therapeutic administration of beta blockers for congestive heart failure ought to begin at very low doses (1⁄8 of target) with a gradual escalation of the dose. The heart of the patient must adjust to decreasing stimulation by catecholamines and find a new equilibrium at a lower adrenergic drive.

Testosterone can be administered by intramuscular injection either as an aqueous suspension of testosterone or as an oil solution or aqueous suspension of testosterone esters such as testosterone propionate, testosterone enanthate, testosterone cypionate, testosterone undecanoate, and testosterone isobutyrate. An even longer-acting testosterone ester that was developed but ultimately never marketed is testosterone buciclate. These preparations are prodrugs of progesterone that have a long-lasting depot effect when injected into muscle or fat, ranging from days to months in duration. The bioavailability of drugs that are administered intramuscularly is generally almost 95%. As oil solutions by intramuscular injection, the elimination half-lives of testosterone esters are 0.8 days for testosterone propionate, 4.5 days for testosterone enanthate, 20.9 days (in tea seed oil) and 33.9 days (in caster oil) for testosterone undecanoate, and 29.5 days for testosterone buciclate. The pharmacokinetics of testosterone cypionate are said to be the same as those of testosterone enanthate, with "extremely comparable" patterns of testosterone release. Due to their varying and different elimination half-lives, the different intramuscular testosterone esters are administered with differing frequencies. Testosterone propionate is injected two to three times per week, testosterone enanthate and testosterone cypionate are injected once every two to four weeks, and testosterone undecanoate and testosterone buciclate are injected once every 10 to 14 weeks.

== Sustainability == Hetero reports its ESG performance annually with reference to the Global Reporting Initiative (GRI), the Sustainability Accounting Standards Board( SASB), and the UN Global Compact. Environment Hetero leads its environment strategy with the stated goal of reaching net zero emissions by 2045. Interim environmental targets include 25% reduction in Scope 1 and Scope 2 emissions by 2030 (with 2022 as a baseline), a 30% increase in the use of renewable energy by 2030, and becoming a Zero Waste to Landfill company in the same year. According to the company’s FY2024-2025 Sustainability report, the company’s Scope 1 emissions were 3,12,435 tCO₂e and Scope 2 emissions were 2,95,020 tCO₂e, resulting in total Scope 1 and Scope 2 emissions of 6,07,455 tCO₂e. Emissions intensity for the year stood at 3.09 tCO₂e per million INR revenue, while biogenic emissions amounted to 72425 tCO₂e. The company also completed its first Scope 3 inventory, covering 13 categories and totalling 1,253,550 tCO₂e. 20% of Hetero’s total energy consumption came from renewable sources. The company recycled 343849 kilolitres of wastewater through Zero Liquid Discharge systems, and recycled 100% of non-hazardous waste, resulting in two sites (Annora and Jeedimetla) receiving Zero Waste to Landfill certification. Social Hetero’s social approach revolves around workforce wellbeing, diversity, inclusion, and occupational safety. As of FY2024-25, Hetero employed 18292 people directly and 10355 people through contract. Women made up 13.63% of direct workforce and 19.28% of contract workers.

Sources: en.wikipedia.org

Supporting material

=== Metal ion binding === Beyond the iron-sulfur proteins, many other metal cofactors in enzymes are bound to the thiolate substituent of cysteinyl residues. Examples include zinc in zinc fingers and alcohol dehydrogenase, copper in the blue copper proteins, iron in cytochrome P450, and nickel in the [NiFe]-hydrogenases. The thiol group also has a high affinity for heavy metals, so that proteins containing cysteine, such as metallothionein, will bind metals such as mercury, lead, and cadmium tightly. Silver ions can also bind tightly to cysteine and cause secondary structure changes in cysteine-containing peptides, e.g. leading to alpha helix formation. This is also the case for zinc fingers in which silver ions can replace zinc and form stable zinc/cysteine clusters with partial alpha helical structure. The extent of alpha helix formation increases with the number of cysteines.

proved the intracellular uptake of cargo via endocytosis, along with cargo release as a result of coiled-coil dissociation. Dr. Ondřej Vaněk and colleagues utilized the same E3/K3-PHPMA system to attach an antibody to the polymer backbone to target the delivery of the drug system, which was successful in vitro. Coiled-coil polymer hybrid drug delivery systems can also be used in drug-free macromolecular therapeutic (DFMT) applications, whereby a coiled-coil-based system would be used to induce apoptosis in target cells. Specifically, Dr. Jindřich Kopeček and colleagues attempted to induce apoptosis in CD20-positive non-Hodgkin's lymphoma B-cells by mimicking the induction of apoptosis typically caused by the recognition of secondary antibodies to the CD20 antigen. In this case, apoptosis was induced upon the oligomerization of a PHMPA copolymer-conjugated coil to the anti-CD20 FAB fragment-conjugated coil (which would recognize and bind CD20). The coiled-coil motifs used in this system were the anti-parallel heterodimeric CCE/CCK coiled coils, which consist of pentaheptad repeats. This system was found to be successful at inducing apoptosis in those cells in vitro, providing an alternative to the anti-CD20 antibody drug Rituximab. Further studies have shown the efficacy of this system in vivo whereby malignant B-cells implanted in the bone marrow of mice were eradicated completely.

== History == Static SIMS was introduced by Benninghoven at the University of Münster in 1969. He applied the technique of SIMS to study surfaces in UHV by deliberately using low primary-ion currents covering large areas. Initially, most SSIMS was performed using quadrupole mass analyzers. However, in the mid-1980s, it was realized that time-of-flight mass spectrometers are more efficient for this mode of SIMS. Compared to other surface techniques, such as Auger and photoelectron spectroscopy, SSIMS offers some unique features, including isotope sensitivity, hydrogen sensitivity, direct compound detection by molecular secondary-ion emission, and extremely high sensitivity, very often in the ppm range. However, one problem in static SIMS applications may be quantification. This problem can be overcome by using a combination of electron-spectroscopic techniques such as Auger electron spectroscopy (AES) and photoelectron spectroscopy (UPS or XPS) with static SIMS.

Sources: en.wikipedia.org

Notes from published material

==== Nuclear reaction ==== During induced fission, a compound system is formed after an incident particle fuses with a target. The resultant excitation energy may be sufficient to emit neutrons, or gamma-rays, and nuclear scission. Fission into two fragments is called binary fission, and is the most common nuclear reaction. Occurring least frequently is ternary fission, in which a third particle is emitted. This third particle is commonly an α particle. Since in nuclear fission, the nucleus emits more neutrons than the one it absorbs, a chain reaction is possible. Binary fission may produce any of the fission products, at 95±15 and 135±15 daltons. One example of a binary fission event in the most commonly used fissile nuclide, 235U, is given as:

Leumorphin, also known as dynorphin B1–29, is a naturally occurring endogenous opioid peptide. Derived as a proteolytic cleavage product of residues 226-254 of prodynorphin (preproenkephalin B), leumorphin is a nonacosapeptide (29 amino acids in length) and has the sequence Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Gln-Phe-Lys-Val-Val-Thr-Arg-Ser-Gln-Glu-Asp-Pro-Asn-Ala-Tyr-Ser-Gly-Glu-Leu-Phe-Asp-Ala. It can be further reduced to dynorphin B (dynorphin B-13) and dynorphin B-14 by pitrilysin metallopeptidase 1 (formerly referred to as "dynorphin-converting enzyme"), an enzyme of the endopeptidase family. Leumorphin behaves as a potent and selective κ-opioid receptor agonist, similarly to other endogenous opioid peptide derivatives of prodynorphin.

== Fecundity == Fecundity of An. gambiae depends on the detoxification of reactive oxygen species (ROS) by catalase. Reduction in catalase activity significantly reduces reproductive output of female mosquitoes, indicating that catalase plays a central role in protecting oocytes and early embryos from ROS damage.

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 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.

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