en · de · es · fr · pt
melanotan-2-notes.peptides6908.com › Faq › Melanotan-2 Identity And Receptor Pharmacology — Worked Examples

Melanotan-2 Identity And Receptor Pharmacology — Worked Examples

By Editorial Desk · published 2025-12-16 · last reviewed 2026-01-21 · Faq

A practical reference on alpha-MSH analog: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.

This page was last updated on 2026-01-21 and is reviewed periodically as new material appears.

Melanotan-2 Identity and Receptor Pharmacology

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.

Peptide Identity and Structural Background

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.

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.

Melanotan-2 at a glance

PropertyValueNotes
Common synonymsMelanotan II; MT-II; N-acetyl-norleucyl-cyclo[Asp-His-D-Phe-Arg-Trp-Lys] amideNaming follows peptide convention; the numeral distinguishes it from melanotan-1
Molecular formulaC50H69N15O9Includes the lactam bridge; no counter-ion assumed
Monoisotopic mass1023.53 DaFree base; salts and counter-ions shift the observed value
AppearanceWhite to off-white lyophilised powderBatch-to-batch colour variation is not itself proof of impurity
Typical analytical methodRP-HPLC purity determination with ESI-MS identity confirmationRetention time alone does not establish sequence identity

Chemistry and Receptor Pharmacology

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.

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.

Related pages on this site

Background and Receptor Mechanism

Published human data come mostly from small, short studies rather than large controlled trials. Reported outcomes include increased skin pigmentation and, in some reports, effects on appetite and libido, but sample sizes are small and follow-up is limited. Whether long-term use produces durable pigment changes or adverse effects is not established. Because products sold outside pharmacies are not standardized, the actual content of any given vial is often unknown. Independent testing of such material is uncommon.

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.

Supporting material

=== Japan === In Japan, drugs and medical devices are given the designation as an orphan drug or device based on the Act of Securing Quality, Efficacy, Safety of Pharmaceuticals, Medical Devices, Regenerative or Cellular Therapy Products, Gene Therapy Products, and Cosmetics if they are intended for use in less than 50,000 patients in Japan for which there is a high medical need.

=== Arboretum === Much of the main campus has been designated an arboretum. Plants from around the world are labeled along a self-guided plant walk. The Krutch Cactus Garden includes the tallest Boojum tree in the state of Arizona. Two herbaria on the university campus are referred to as "ARIZ" in the Index Herbarium. The campus also boasts hundreds of olive trees many of which were planted by Prof. Robert H. Forbes. Many of these trees are over a hundred years old.

=== Intraocular viscoelastic injection === It is used as an aid in ophthalmic surgery acting as aqueous and vitreous humor, e.g. in cataract extraction (intra- and extracapsular), intraocular lens implantation, corneal transplant, glaucoma filtration, and retina attachment surgery and in the treatment of dry eyes. In surgical procedures in the anterior segment of eyeball, instillation of sodium hyaluronate its viscoelasticity enables maintenance of a deep chamber during surgical manipulation since the solution does not flow out of the open anterior chamber, allowing for efficient manipulation with less trauma to the corneal endothelium and other surrounding tissues. Its viscoelasticity also helps to push back the vitreous face and prevent formation of a postoperative flat chamber. In posterior segment surgery, sodium hyaluronate serves as a surgical aid to gently separate, maneuver, and hold tissues. It creates a clear field of vision, facilitating intra-operative and post-operative inspection of the retina and photocoagulation.

==== Native Hawaiian or other Pacific Islander ==== The obesity rate for Native Hawaiian or other Pacific Islander adults (over 30 BMI) in the US in 2015 was 33.4%. No breakdown by sex was given for Native Hawaiian or other Pacific Islander adults in the CDC figures.

Increased demand for iron, which the diet cannot accommodate. Increased loss of iron (usually through loss of blood). Nutritional deficiency. This can result due to a lack of dietary iron or consumption of foods that inhibit iron absorption. Absorption inhibition has been observed caused by phytates in bran, calcium from supplements or dairy products, and tannins from tea, although in all three of these studies the effect was small and the authors of the studies cited regarding bran and tea note that the effect will probably only have a noticeable impact when most iron is obtained from vegetable sources. Acid-reducing medications: Acid-reducing medications reduce the absorption of dietary iron. These medications are commonly used for gastritis, reflux disease, and ulcers. Proton pump inhibitors (PPIs), H2 antihistamines, and antacids will reduce iron metabolism. Damage to the intestinal lining. Examples of causes of this kind of damage include surgery involving the duodenum or diseases like Crohn's disease or celiac sprue which severely reduce the surface area available for absorption. Helicobacter pylori infections also reduce the availability of iron. Inflammation leading to hepcidin-induced restriction on iron release from enterocytes (see above). Is also a common occurrence in pregnant women, and in growing adolescents due to poor diets. Acute blood loss or acute liver cirrhosis creates a lack of transferrin therefore causing iron to be secreted from the body.

Sources: en.wikipedia.org

Notes from published material

7 December Storm Darragh: Hundreds of thousands are left without power, while travel is disrupted and many planned events are called off, as winds of up to 93 mph (150 km/h) hit much of the UK, along with heavy rain. A rare red weather warning is in place in Wales and south-west England, meaning the storm poses a risk to life. The deaths of two men are reported, in Birmingham and Lancashire, due to trees falling on vehicles. A 61-year-old Elizabeth line worker dies following a serious assault at Ilford railway station on 4 December. A 28-year-old man is charged with grievous bodily harm, affray, and possession of a prohibited offensive weapon. 8 December Prime Minister Sir Keir Starmer welcomes the Fall of the Assad regime in Syria, which he describes as "barbaric", and calls for the restoration of "peace and stability". Emma Pinchbeck, the new chief executive of the UK government's Climate Change Committee, says the UK is "not ready" for the kind of extreme weather brought by Storm Darragh. Prince William helps to serve lunch at The Passage, a London-based homeless charity he first visited with his mother as a boy. 9 December – The UK pauses asylum claims from Syrian refugees following the overthrow of Bashar al-Assad. 10 December The UK government recommends a 2.8% pay rise for public sector workers from April 2025. In response, the Unison trade union describes the offer as "barely above the cost of living". King Charles III presents the first Elizabeth Emblems, recognising public servants such as police officers and firefighters who died while on duty.

== Chemistry == Anastrozole is a nonsteroidal benzyl triazole. It is also known as α,α,α',α'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile. Anastrozole is structurally related to letrozole, fadrozole, and vorozole, with all being classified as azoles.

One paragraph had "Regenerative Medicine" as a bold print title and stated, "A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems." The term was brought into the popular culture in 1999 by William A. Haseltine when he coined the term during a conference on Lake Como, to describe interventions that restore to normal function that which is damaged by disease, injured by trauma, or worn by time. Haseltine was briefed on the project to isolate human embryonic stem cells and embryonic germ cells at Geron Corporation in collaboration with researchers at the University of Wisconsin–Madison and Johns Hopkins School of Medicine. He recognized that these cells' unique ability to differentiate into all the cell types of the human body (pluripotency) had the potential to develop into a new kind of regenerative therapy. Explaining the new class of therapies that such cells could enable, he used the term "regenerative medicine" in the way that it is used today: "an approach to therapy that ... employs human genes, proteins and cells to re-grow, restore or provide mechanical replacements for tissues that have been injured by trauma, damaged by disease or worn by time" and "offers the prospect of curing diseases that cannot be treated effectively today, including those related to aging".

The mechanism for the reaction is similar to that of other dioxygenases, and occurs in two distinct stages: In the first, a highly reactive Fe(IV)=O species is produced. Molecular oxygen is bound end-on in an axial position, producing a dioxygen unit. Nucleophilic attack on C2 generates a tetrahedral intermediate, with loss of the double bond in the dioxygen unit and bonds to iron and the alpha carbon of 2-oxoglutarate. Subsequent elimination of CO2 coincides with the formation of the Fe(IV)=O species. The second stage involves the abstraction of the pro-R hydrogen atom from C-4 of the proline substrate followed by radical combination, which yields hydroxyproline. As a consequence of the reaction mechanism, one molecule of 2-oxoglutarate is decarboxylated, forming succinate. This succinate is hydrolyzed and replaced with another 2-oxoglutarate after each reaction, and it has been concluded that in the presence of 2-oxoglutarate, enzyme-bound Fe2+ is rapidly converted to Fe3+, leading to inactivation of the enzyme. Ascorbate is utilized as a cofactor to reduce Fe3+ back to Fe2+.

Sources: en.wikipedia.org

Frequently asked questions

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.

How does it differ from the natural hormone?

The natural hormone is a linear tridecapeptide that is rapidly degraded in circulation. Melanotan-2 is shortened, cyclised, N-terminally acetylated, and carries a D-amino acid substitution, all of which slow enzymatic breakdown.

Does it hold any regulatory approval?

No national medicines regulator has approved melanotan-2 for therapeutic or cosmetic use. In several jurisdictions it is treated as an unapproved prescription medicine, and its legal classification differs from country to country.

What is Melanotan-2 chemically?

It is a synthetic cyclic heptapeptide and an analogue of alpha-melanocyte-stimulating hormone. The molecule is produced by chemical synthesis rather than extracted from a biological source.

Network