This is a working overview of alpha-MSH, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2025-12-19 and is reviewed periodically as new material appears.
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.
Identity and purity are usually assessed by reversed-phase high-performance liquid chromatography, which separates the target peptide from truncated or oxidised impurities. Mass spectrometry, most often coupled to liquid chromatography, confirms molecular mass and detects substitutions that chromatography alone may miss. Amino acid analysis and peptide mapping supply additional structural evidence, while nuclear magnetic resonance is reserved for full structural confirmation. Laboratories that examine samples sold online report wide variation in actual content, with some vials containing little or none of the labelled material.
Melanotan-2 appears on the World Anti-Doping Agency prohibited list within the peptide hormone class, and several national regulators treat it as an unapproved prescription substance. Some countries restrict importation or sale for personal use. Because the compound is widely traded as a research chemical, the practical legal picture differs between jurisdictions and shifts over time. Human safety data covering long periods are limited, and whether repeated pigmentation changes carry any lasting risk to melanocytes remains an open question.
Freeze-dried melanotan-2 is normally kept as a desiccated powder at minus twenty degrees Celsius or lower, shielded from light and moisture. Peptides of this size degrade through hydrolysis, oxidation and deamidation, and each pathway accelerates as temperature and water activity rise. Repeated freeze-thaw cycles promote aggregation and loss of material, so aliquoting a stock solution before freezing is standard laboratory practice. Once dissolved, the solution is markedly less stable than the powder. In laboratory work, solutions are generally refrigerated and used within days rather than kept for months.
| Property | Value | Notes |
|---|---|---|
| Compound class | Synthetic cyclic heptapeptide | Alpha-MSH analogue containing a D-phenylalanine residue |
| Molecular formula | C50H69N15O9 | Average molecular mass approximately 1024.2 g/mol |
| Appearance | White to off-white lyophilised powder | Normally supplied as a freeze-dried solid in a sealed vial |
| Solubility | Freely soluble in water and polar solvents | Dissolves readily in aqueous buffers and in alcohol-water mixtures |
| Receptor targets | MC1R, MC3R, MC4R, MC5R | Acts as a non-selective melanocortin receptor agonist |
Regulatory treatment varies between countries. Several national medicines agencies have classified the peptide as unapproved, and customs authorities in some jurisdictions seize shipments on that basis. A few jurisdictions channel supply through prescription-only frameworks that do not list the substance by name. Because the material circulates mainly through online vendors, composition and purity are rarely verified before sale. Surveys of unapproved peptide products have reported labels that did not match measured content in a substantial fraction of samples.
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.
Solid peptide kept dry at minus twenty degrees Celsius, shielded from light and moisture, is generally considered stable for extended periods. Solutions are divided into single-use aliquots and held at minus twenty or minus eighty degrees Celsius, because repeated freeze-thaw cycles promote aggregation and loss of material to container surfaces. Hydrolysis of the backbone and oxidation of tryptophan are the principal degradation routes in aqueous solution, and both accelerate at ambient temperature. Hygroscopic uptake after a vial is opened can also shift the actual mass weighed, which affects any concentration calculated from it.
Routine characterisation relies on reversed-phase high-performance liquid chromatography with ultraviolet detection near 214 nanometres, using a C18 column and a water-acetonitrile gradient containing trifluoroacetic acid. Electrospray ionisation mass spectrometry confirms the expected molecular mass and can reveal truncated or oxidised by-products that co-elute poorly. Sequence and stereochemistry require additional work, such as peptide mapping or amino acid analysis, because a chromatographic purity figure alone does not distinguish a diastereomer from the target peptide. Independent testing of research-grade material frequently shows measured content below the stated label, so a certificate of analysis is best read together with the method that produced it.
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.
Melanotan-2 has not received marketing authorisation from major regulatory agencies for any therapeutic indication. Several jurisdictions classify it as a prescription-only medicine or a controlled substance when supplied for human use. Because approved products do not exist, material sold online usually sits outside pharmaceutical supply chains and formal quality oversight. Regulators have issued public notices describing the compound as unapproved. Enforcement varies, and the legal position differs between countries, which complicates any single general statement about its status.
Scientific discussion of Melanotan-2 spans pharmacology, dermatology, and public-health literature. Laboratory studies examine its receptor binding and cellular effects, while clinical reports describe outcomes observed after unregulated use. These two bodies of work differ in rigour and intent. Peer-reviewed trials of the compound as a medicine are limited, so much of the available information comes from case reports and surveillance data. Authors frequently note the gap between experimental findings and real-world use.
Reported observations after unregulated use include shifts in skin pigmentation and, in some accounts, unintended changes to moles and other lesions. Whether these outcomes are causally linked to the compound, and how often they occur, remain open questions because controlled data are scarce. The absence of standardised dosing and verified product purity complicates interpretation. Researchers have called for better surveillance and analytical characterisation of samples obtained outside regulated channels. Conclusions drawn from anecdotal evidence should be treated as provisional.
Encroachment on wildlife habitats. The construction of new villages and housing developments in rural areas force animals to live in dense populations, creating opportunities for microbes to mutate and emerge. Changes in agriculture. The introduction of new crops attracts new crop pests and the microbes they carry to farming communities, exposing people to unfamiliar diseases. The destruction of rain forests. As countries make use of their rain forests, by building roads through forests and clearing areas for settlement or commercial ventures, people encounter insects and other animals harboring previously unknown microorganisms. Uncontrolled urbanization. The rapid growth of cities in many developing countries tends to concentrate large numbers of people into crowded areas with poor sanitation. These conditions foster transmission of contagious diseases. Modern transport. Ships and other cargo carriers often harbor unintended "passengers", that can spread diseases to faraway destinations. While with international jet-airplane travel, people infected with a disease can carry it to distant lands, or home to their families, before their first symptoms appear.
== Construction of PAM matrices == PAM matrices were introduced by Margaret Dayhoff in 1978. The calculation of these matrices was based on 1572 observed mutations in the phylogenetic trees of 71 families of closely related proteins. The proteins to be studied were selected on the basis of having high similarity with their predecessors. The protein alignments included were required to display at least 85% identity. As a result, it is reasonable to assume that any aligned mismatches were the result of a single mutation event, rather than several at the same location. Each PAM matrix has twenty rows and twenty columns — one representing each of the twenty amino acids translated by the genetic code. The value in each cell of a PAM matrix is related to the probability of a row amino acid before the mutation being aligned with a column amino acid afterwards. From this definition, PAM matrices are an example of a substitution matrix.
The discovery in 1911 that electrons emitted in beta decay have a continuous rather than a discrete spectrum appeared to contradict conservation of energy, under the then-current assumption that beta decay is the simple emission of an electron from a nucleus. This problem was eventually resolved in 1933 by Enrico Fermi who proposed the correct description of beta-decay as the emission of both an electron and an antineutrino, which carries away the apparently missing energy.
=== Asprosin === Obesity is characterized by an overall increase in adiposity and, given that asprosin is secreted by adipose tissue, it is not surprising that both obese humans and mice show pathologically elevated levels of asprosin compared with control subjects. Patients presenting with insulin resistance and obesity have elevated serum levels of asprosin, and female patients with polycystic ovary syndrome have particularly high serum levels. Obese patients undergoing bariatric surgery for weight loss show decreased asprosin levels in serum after surgery. Asprosin-induced hyperphagia and hepatic glucose production could therefore be mechanisms that drive development of metabolic syndrome.
Sources: en.wikipedia.org
During the fall of 1924, Marvel found him a job as an assistant biochemist at the Philadelphia General Hospital that helped him to teach clinical chemistry at the Graduate School of Medicine, University of Pennsylvania. Marvel would pay for the trip to Pennsylvania in exchange for du Vigneaud's preparation of 10 pounds of cupferron. Resuming his academic career in 1925, du Vigneaud joined the group of John R. Murlin at the University of Rochester for his PhD thesis. He graduated in 1927 with his work The Sulfur of Insulin. After a post-doctoral position with John Jacob Abel at Johns Hopkins University Medical School (1927–1928), he traveled to Europe as a National Research Council Fellow in 1928–1929, where he worked with Max Bergmann and Leonidas Zervas at the Kaiser Wilhelm Institute for Leather Research in Dresden, and with George Barger at the University of Edinburgh Medical School. He then returned to the University of Illinois as a professor. In 1932, he started working at the George Washington University Medical School in Washington, D.C., and in 1938, he attended the Cornell Medical College in New York City, where he stayed until his emeritation in 1967. Following retirement, he held a position at Cornell University in Ithaca, New York. In 1974, du Vigneaud had a stroke which forced his retirement. He died in 1978, one year after his wife's death in 1977.
== Treatment == Emerging therapies for genetic skeletal dysplasias include enzyme replacement therapy, small molecule therapy, hematopoietic stem cell transplantation and gene therapy. These therapies aim at preventing disease progression and thus improving quality of life. Enzyme replacement therapies are some of the mucopolysaccharidoses and Gaucher disease. Results have shown effectivity of enzyme replacement therapy. Hematopoietic stem cell transplantation can be lifesaving for some disorders, such as with malignant infantile osteopetrosis. Even with treatments such as enzyme replacement therapy and stem cell transplantation, people with skeletal dysplasia often require orthopedic surgery and other disease management interventions. There is a lack of information available to support these patients as most physicians may only see one or two skeletal dysplasia patients in their lifetime. Guidelines are available to support best practices for managing several areas of skeletal dysplasia, such as the craniofacial aspects of skeletal dysplasia, spinal disorders, diagnosis and management of type II collagen disorders, pregnancy of people with skeletal dysplasia, peri-operative management, and foramen magnum stenosis in achondroplasia. Written and video resources for patients with skeletal dysplasia and caregivers are also available.
== Interaction with integrin α2β1 == Cellular receptors for collagens belong to the family of β1 integrins. Collagen XXIII interacts in an ion-and conformation-dependent manner with integrin α2β1. Integrin α2β1 is a collagen-binding integrin present at the epidermis, therefore this is the location where the interaction takes place. Both proteins co-localize on basal keratinocytes surface.
Instead, they stretch to compensate for dead cells which reduces the overall cell density of the endothelium, which affects fluid regulation. If the endothelium can no longer maintain a proper fluid balance, stromal swelling due to excess fluids and subsequent loss of transparency will occur and this may cause corneal edema and interference with the transparency of the cornea and thus impairing the image formed. Iris pigment cells deposited on the corneal endothelium can sometimes be washed into a distinct vertical pattern by the aqueous currents - this is known as Krukenberg's Spindle.
== Clinical significance == Mutations in the COL2A1 gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer–Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia.
Sources: en.wikipedia.org
== Immunoglobulin-like receptors == Glycoprotein VI Receptor GPVI belongs to immunoglobulin family of glycoproteins. It consists of two extramembrane immunoglobulin domains, which are associated with extracellular glycosylated mucine and together they form a stalk. Another part of the receptor consists of transmembrane helix with a short cytosolic domain. A FcRγ chain with ITAM (immunoreceptor tyrosine-based activation motif) domain is associated with the transmembrane domain. The short cytosolic domain interacts with calmodulin and Src kinases Lyn and Fyn. These Src kinases phosphorylate tyrosine in ITAM domain and activate a signalling cascade. Glycoprotein VI belongs to collagen receptors that are primarily expressed on platelets surface. Together with integrin receptor α2β1 they provide coagulation cascade activation when a blood-vessel is damaged. When damage occurs, endothelial collagen is uncovered and is bound by GPVI receptor on platelets. This interaction activates signalling cascades leading to coagulation factors release. Mainly fibrillar collagens type I and III serve as ligands. Functions include: Platelet adhesion and activation - the most important platelet collagen receptor in terms of signaling. LAIR1(Leukocyte-associated IG-like receptor) works as inhibition signal for different immune cells. Lair-1 consists of Ig domain, transmembrane helix and a short cytosolic domain, which includes two inhibition motifs (ITIMs), which can block tyrosine domain when activated.
=== Congenital cataract === In humans, a novel mutation of the COL4A1 gene coding for collagen type IV was found to be associated with autosomal dominant congenital cataract in a Chinese family. This mutation was not found in unaffected family members or in 200 unrelated controls. In this study, sequence analysis confirmed that the Gly782 amino acid residue was highly conserved. This report of a new mutation in the COL4A1 gene is the first report of a non-syndromic autosomal dominant congenital cataract that highlights an important role for collagen type IV in the physiological and optical properties of the lens.
=== Availability === Lemborexant is marketed in the United States, Canada, Australia, and Japan. It is not approved by the European Medicines Agency (EMA) for use in the European Union or by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom.
According to results presented at the 2018 meeting of the American Diabetes Association, Afrezza increases the time that blood glucose levels remain in the optimal range (74–106 mg/dl), reducing both spikes in blood glucose and time in hypoglycemia in adults with type 1 diabetes, compared to insulin aspart.
Sources: en.wikipedia.org
No. It is a laboratory-made peptide, while the natural hormone is alpha-melanocyte-stimulating hormone, a longer peptide produced by the pituitary gland and by skin cells. Melanotan-2 mimics only a short active region of that hormone and contains non-natural residues such as D-phenylalanine.
No approved regulatory indication exists in major markets. An approval exists for a different peptide, afamelanotide, which is used for a rare photosensitivity disorder called erythropoietic protoporphyria. Melanotan-2 itself remains a research compound with no cleared clinical role.
Melanocortin-1 receptors on melanocytes are the receptor most closely linked to pigment production. The peptide is not selective, however, and also activates melanocortin-3, melanocortin-4, and melanocortin-5 receptors. That lack of selectivity is the usual explanation offered for both its range of observed effects and its off-target effects.
The lyophilised solid is best kept cold, dry and dark, typically at minus twenty degrees Celsius. Moisture and repeated warming cycles are the main causes of degradation. Solutions prepared from the powder are less stable and are normally used quickly.