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Melanotan-2 Structure And Receptor Pharmacology — Reference Sheet

By Editorial Desk · published 2025-07-30 · last reviewed 2025-08-28 · Info

cyclic heptapeptide raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.

Reviewed 2025-08-28. Anything still debated is marked as such rather than presented as settled.

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 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.

Origins and Research Status

Melanotan II is a synthetic peptide analog modeled on alpha-melanocyte-stimulating hormone, a naturally occurring signaling peptide involved in pigmentation. Its structure is a cyclic heptapeptide containing two non-natural substitutions, norleucine at position four and D-phenylalanine at position seven. These modifications resist enzymatic breakdown and extend the molecule's activity relative to the native hormone. The compound binds melanocortin receptors and is studied mainly as a pharmacological tool rather than a therapeutic product. It has never received approval as a medicine in any major jurisdiction.

The compound was developed in the late 1980s and 1990s by academic researchers investigating photoprotection. The rationale held that stimulating melanin production might reduce ultraviolet damage to skin and lower skin cancer risk. Early work examined receptor binding, pigment response, and short-term tolerability in small studies. That program did not produce an approved drug, and formal development stalled after early-phase trials. Whether induced pigmentation confers meaningful photoprotection remains an open question.

Outside regulated medicine, melanotan II circulates through online vendors as a research chemical, often marketed for tanning. Products sold this way vary widely in purity, concentration, and labeling accuracy, and independent testing has documented discrepancies. Published reports describe both pigment effects and adverse reactions, including nausea, flushing, and darkening of existing moles. Long-term safety data are sparse, and no large controlled trial has established a risk profile. Questions about cumulative effects on melanocytes remain unresolved in the literature.

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

Reference notes

=== GLC (1981–1985) === The equivalent American Mazda GLC (Great Little Car) appeared in the 1981 model year, although the rear-wheel drive wagon also continued to be offered. It was only offered with a single engine – the twin-barrel 1.5-litre with 68 hp (51 kW)—and lasted through 1985, after which it was replaced by the next-generation Mazda 323. With this, the GLC nameplate was retired. The BD was the only front-wheel drive Mazda vehicle using the GLC name. Originally it was offered with three- or five-door bodywork, in standard, Custom, Custom L, or Sport equipment levels. The five-door only came as a Custom and was sold only in Hawaii and Puerto Rico. All cars received exposed rectangular sealed-beam units. The later four-door saloon, introduced for 1983, was available in Custom, Custom L, and Sport models. The Sport received blacked out trim, a steering wheel borrowed from the RX-7, full instrumentation, and a special rear interior which closely integrates the side trim with the rear seat design – an early iteration of a design philosophy taken to its extreme with the 1988 Persona and the 1990 Eunos Cosmo. Unlike the sporting 323s in other markets, the Sport only received special hubcaps, rather than alloy wheels. For 1982, the Sport was made to live up to its name a little bit more, with the installation of a front anti-roll bar and cast aluminum wheels. The five-door GLC gained a fully carpeted trunk for 1982.

=== Pregnancy === In women with known hypothyroidism who become pregnant, it is recommended that serum TSH levels are closely monitored. Levothyroxine should be used to keep TSH levels within the normal range for that trimester. The first-trimester normal range is below 2.5 mIU/L and the second and third trimesters normal range is below 3.0 mIU/L. Measurement of free T4 in pregnancy is not recommended due to changes in levels of serum protein binding. Similarly to TSH, the thyroxine results should be interpreted according to the appropriate reference range for that stage of pregnancy. The levothyroxine dose often needs to be increased after pregnancy is confirmed, although this is based on limited evidence and some recommend that it is not always required; decisions may need to based on TSH levels. Women with anti-TPO antibodies who are trying to become pregnant (naturally or by assisted means) may require thyroid hormone supplementation even if the TSH level is normal. This is particularly true if they have had previous miscarriages or have been hypothyroid in the past. Supplementary levothyroxine may reduce the risk of preterm birth and possibly miscarriage. The recommendation is stronger in pregnant women with subclinical hypothyroidism (defined as TSH 2.5–10 mIU/L) who are anti-TPO positive, in view of the risk of overt hypothyroidism. If a decision is made not to treat, close monitoring of the thyroid function (every 4 weeks in the first 20 weeks of pregnancy) is recommended.

One rack unit (U) is 1.75 inches (44.45 mm) and is used to measure rack-mountable audiovisual, computing and industrial equipment. Rack units are typically denoted without a space between the number of units and the 'U'. Thus, a 4U server enclosure (case) is nominally seven inches (177.8 mm) high, or more precisely, built to occupy a vertical space seven inches high, with sufficient clearance to allow movement of adjacent hardware.

Sources: en.wikipedia.org

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Reference notes

== External links == Rudra MN, Chowdhury LM (30 September 1950). "Methionine Content of Cereals and Legumes". Nature. 166 (568): 568. Bibcode:1950Natur.166..568R. doi:10.1038/166568a0. PMID 14780151. S2CID 3026278.

=== Transcriptional regulation === Histones can be ubiquitinated, usually in the form of monoubiquitylation, although polyubiquitylated forms do occur. Histone ubiquitylation alters chromatin structure and allows the access of enzymes involved in transcription. Ubiquitin on histones also acts as a binding site for proteins that either activate or inhibit transcription and also can induce further post-translational modifications of the protein. These effects can all modulate the transcription of genes.

Shotwell (1922–1998), organic chemist Jean'ne Shreeve (born 1933), American organic chemist Dorothy Martin Simon (1919–2016), American physical chemist Susan Solomon (born 1956), Atmospheric chemist JoAnne Stubbe (born 1946), American biochemist Ida Noddack Tacke (1896–1978), German chemist and physicist Tsippy Tamiri (1952-2017), Israeli chemist Giuliana Tesoro (1921–2002), Polymer chemist Margaret Thatcher (1925–2013), British chemist and Prime Minister Jean Thomas, British biochemist (chromatin) Martha J. B. Thomas (1926–2006), Analytical chemist and chemical engineer Ann E. Weber, American organic/medicinal chemist Karen Wetterhahn (1948–1997), American metal toxicologist Ruth R. Wexler (born 1955), American organic and medicinal chemist, discoverer of two marketed drugs M. Christina White (born 1970), American organometallic chemist Charlotte Williams, English inorganic chemist Angela K. Wilson, American computational, theoretical, and physical chemist Ruby K. Worner (1900–1995), American chemist and textiles expert Rosalyn Sussman Yalow (1921–2011), American biochemist Jenara Vicenta Arnal Yarza (1902–1960), Spanish chemist Jean Youatt (born 1925), Australian chemist, biochemist, and microbiologist Ada Yonath (born 1939), Israeli crystallographer, Nobel prize in chemistry 2009 Glaci Zancan (1935–2007), Brazilian biochemist, president of the Brazilian Society for the Progress of the Science (SBPC) from 1999 to 2003

Sources: en.wikipedia.org

Notes from published material

== History == Opicapone was authorised for medical use in the European Union in June 2016. In February 2017, its developer Bial sold exclusive marketing rights for the United States and Canada to Neurocrine Biosciences for an initial payment of US$30 million. Opicapone was authorised for medical use in the United States in April 2020. Opicapone was approved based on evidence from two clinical trials (Trial 1/ NCT01568073, and Trial 2/NCT01227655) of 522 participants with Parkinson's disease (PD) whose symptoms were not well controlled while receiving their regular PD treatment. Trial 1 was conducted at 104 sites in 19 European countries, and Trial 2 was conducted at 69 sites in Argentina, Australia, Belgium, Chile, Czech Republic, Estonia, India, Israel, South Korea, Russia, South Africa and UK. There were two 12-week trials conducted in Parkinson's disease (PD) participants with inadequate control of their Parkinson's symptom ("off" time) while receiving carbidopa/levodopa PD medications. Participants were randomly selected to receive either opicapone or a placebo capsule once a day. Neither the participants nor the health care providers knew which treatment was being given until the trial was completed. In all of the trials, the participants kept daily diaries of the number of hours of "off" time for the three days before the evaluation visit. The benefit was evaluated by measuring the change from baseline in total daily "off" time in opicapone- and placebo-receiving participants.

=== Transitioning to commercial release (2013–2014) === A new version of the Source engine had been introduced by 2013 that, in addition to new engine features, included support for OS X and Linux platforms. However, developers had to pay to gain access to the full feature set of this engine. According to Adam Engels, the project lead at the completion of Black Mesa, Valve approached their team around this time and suggested making Black Mesa a commercial release and, thus, getting a license to the Source engine. The team considered this option, and, since access to the full Source engine would help make Black Mesa the best game they could, opted to go the commercial route to be able to pay for that license, not having originally intended to profit from the game. By November 2013, the team had affirmed that they had gotten Valve's permission to sell the game. Some of the team were later invited to Valve's offices in Bellevue, Washington in 2015. At this point in 2013, the team cautioned that a final version was still some distance away, as they were still dealing with the updated Source engine, and they had not yet done much with Xen. Crowbar Collective continued to offer the free version of Black Mesa, based on the earlier Source engine, on their website. With the new Source engine, the team started to look more closely at how Valve had used Source in Half-Life 2, compared to what they had done in the original Half-Life, and developed changes for Black Mesa that reflected what they believed were Valve's design principles in Half-Life 2.

==== Role in myocardial growth and adaptation ==== Intracrine PTHrP has been implicated in myocardial development and adaptation to stress. It is particularly active during embryonic heart development, where it influences cardiomyocyte differentiation and growth. Additionally, under conditions of cardiac stress, such as ischemia or hypertrophy, PTHrP expression is upregulated, suggesting a protective role in maintaining myocardial function. Moreover, in vascular smooth muscle cells, intracrine PTHrP plays a dual role. While secreted PTHrP can inhibit cell proliferation via receptor-mediated pathways, intracellular PTHrP exerts a mitogenic effect, promoting vascular remodeling and adaptation in response to hemodynamic changes.

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 II?

It is a synthetic cyclic peptide designed as an analog of alpha-melanocyte-stimulating hormone. It acts on melanocortin receptors and is best known from research into pigmentation. It is not an approved pharmaceutical product.

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