Everything below concerns cyclic peptide. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2025-12-09. Numbers and descriptions here follow the published literature rather than marketing material.
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.
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.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C50H69N15O9 | Synthetic cyclic heptapeptide |
| Molecular mass | Approximately 1024 g/mol | Depends on counter-ion content |
| Appearance | White to off-white powder | Commonly supplied as a lyophilised solid |
| Solubility | Freely soluble in water | Also dissolves in common aqueous buffers |
| Typical storage | -20 degrees Celsius, desiccated | Protect from light and repeated freeze-thaw |
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.
Lyophilised melanotan-2 is supplied as a solid, which is more stable than a solution. The material is hygroscopic, so weighing is done quickly, in low humidity, with the container kept sealed. Reconstitution usually uses water for injection or bacteriostatic water, added down the wall of the vial to limit foaming. A reconstituted solution is held at 2 to 8 °C and kept away from light. Repeated freezing and thawing of the same vial is avoided because ice crystal formation and concentration effects degrade the peptide.
Reversed-phase high-performance liquid chromatography is the routine method for purity assessment. Peptides absorb near 214 nm because of the peptide bond, and a gradient of acetonitrile in water separates the intact peptide from deletion sequences, oxidised products, and earlier-eluting fragments at neutral pH. Electrospray ionisation mass spectrometry provides an orthogonal check: the measured mass must agree with the theoretical value. Amino acid analysis and peptide mapping confirm structure but are used less often. Reference standards remain scarce because the peptide is not described in any pharmacopoeia.
Melanotan II binds several melanocortin receptor subtypes rather than a single target. MC1R on melanocytes drives melanin synthesis, while MC3R and MC4R participate in energy balance, appetite, and sexual response pathways. This lack of selectivity explains why reported effects extend beyond skin darkening. Substitutions at positions four and seven, including norleucine and D-phenylalanine, increase potency and resistance to peptidases. Understanding which receptor mediates which effect remains an active area of investigation.
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.
=== 20 November === The Awlad Gammari (Sons of Gamari), an SAF-allied militia group based in Dongola, staged a mutiny, resulting in clashes with the SAF that left two people dead. The European Union imposed sanctions on Abdul Rahim Dagalo for violations committed by the RSF in Darfur.
== Relation to C-reactive protein == C-reactive protein (CRP) is an acute phase protein. Therefore, it is a better marker for acute phase reaction than ESR. While ESR and CRP generally together correlate with the degree of inflammation, this is not always the case and results may be discordant in 12.5% of the cases. Cases with raised CRP but normal ESR may demonstrate a combination of infection and some other tissue damage such as myocardial infarction, and venous thromboembolism. Such inflammation may not be enough to raise the level of ESR. Those with high ESR usually do not have demonstrable inflammation. However, in cases of low grade bacterial infections of bone and joints such as coagulase negative staphylococcus (CoNS), and systemic lupus erythematosus (SLE), ESR can be a good marker for the inflammatory process. This may be due to the production of Interferon type I that inhibits the CRP production in liver cells during SLE. CRP is a better marker for other autoimmune diseases such as polymyalgia rheumatica, giant cell arteritis, post-operative sepsis, and neonatal sepsis. ESR may be reduced in those who are taking statins and non-steroidal anti-inflammatory drugs (NSAIDs).
== History == Orexigen Therapeutics submitted a New Drug Application (NDA) for the combination to the FDA in March 2010. Having paid a fee under the Prescription Drug User Fee Act, Orexigen was given a deadline for the FDA to approve or reject the drug of January 2011. In December 2010, an FDA Advisory Committee voted 13–7 to approve Contrave and 11–8 to conduct a post-marketing cardiovascular outcomes study. Subsequently, on 2 February 2011, the FDA rejected the drug, and it was decided that an extremely large-scale study of the long-term cardiovascular effects of Contrave would be needed before approval could be considered. It was ultimately approved in the United States in 2014. In December 2014, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency endorsed the combination for licensure as an obesity medication when used alongside diet and exercise. Authorization was granted in March 2015. A review of Mysimba was completed by the CHMP in March 2025. In May 2015, Orexigen prematurely ended the trial that was intended to test whether naltrexone/bupropion increased the risk of major adverse cardiovascular events in obese patients with cardiovascular disease because an independent panel of experts said that the drug maker "inappropriately" compromised the trial by prematurely releasing interim data. The early data release reported a reduction in heart attacks, but that advantage was no longer observed when a more complete view of the data was analyzed.
== Structure and reactivity == κ-Bungarotoxin has a single polypeptide chain consisting of 66 amino acids. The overall weight of this chain is 7313 DA. Two single polypeptide chains can arrange together into a dimer. The subunit of the dimer consists of three main chain loops. These loops have a rotation of 178.6 degrees. Overall, κ-bungarotoxin has ten beta strands. This forms a six stranded antiparallel beta sheet configuration[8]. This is formed by three out of the five beta strands of each subunit of the dimer. Arg 34 is at the top of the central loop for each subunit. The outer strand of loop III is involved in an antiparallel arrangement. The κ-bungarotoxin dimer can make disulfide bonds, hydrogen bonds and van der Waals connections.
Transition options for transgender adolescents and youth are significantly limited compared to those for transgender adults. Prepubescent transgender youth can go through various social changes, such as presenting as their gender and asking to be called by a different name or different pronouns. Medical options for transition become available once the child begins to enter puberty. Under close supervision by a team of doctors, puberty blockers may be used to limit the effects of puberty. Discrimination has a significant effect on the mental health of young transgender people. The lack of family acceptance, rejection in schools and abuse from peers can be powerful stressors, leading to poor mental health and substance abuse. A study done on transgender youth in San Francisco found that higher rates of both transgender-based and racial bias are associated with increased rates of depression, post-traumatic stress disorder, and suicidal ideation. The Swiss National Advisory Commission on Biomedical Ethics (NCE) has suggested that research into treatments for gender-incongruent and gender-diverse young people should routinely consider the impact of social factors, including discrimination and social support, when analyzing their results. In a 2018 review, evidence suggested that hormonal treatments for transgender adolescents can achieve their intended physical effects.
Sources: en.wikipedia.org
White sharks are estimated to swim 2.88–4.86 km/h (1.79–3.02 mph) but can sprint up to 24.12 km/h (14.99 mph). One individual was recorded cruising at a sustained speed of 4.7 km/h (2.9 mph) while migrating, which is fast for a shark and more similar to fast-swimming tuna. White sharks display various surface behaviors. These include spyhopping (poking head out of the surface) to observe an object above the water, as well as 'repetitive aerial gaping' where a spyhopping shark repeatedly gapes its mouth while belly-up, possibly as a sign of frustration after missing a bait. How they sleep is not well understood. At night, one individual was recorded swimming slowly in one direction along a current with its mouth open. The white shark is generally considered to be a solitary species, though aggregations do occur. A 2016 study of sharks around Mossel Bay, South Africa, concluded that white shark associations are generally random with few social interactions. By contrast, a 2019 study found that sharks around Neptune Islands gathered in non-random aggregations. Similarly, a 2022 study of white sharks at Guadalupe Island suggested that individuals may associate so that they can learn from others where to find prey or carcasses to scavenge. White shark aggregations can consist of individuals of a specific age and sex. At Neptune Islands, sightings of subadult females peak during April and May, subadult males in February and again in September, adult females in June, and adult males in September.
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP+, is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require it as a reducing agent ('hydrogen source'). NADPH is the reduced form, whereas NADP+ is the oxidized form. The reduced form, NADPH is used by all forms of cellular life as an electron donor as part of many biosynthetic reactions. NADP+ differs from NAD+ by the presence of an additional phosphate group on the 2' position of the ribose ring that carries the adenine moiety. This extra phosphate is added by NAD+ kinase and removed by NADP+ phosphatase. As cofactors for enzyme reactions in mammals, NAD+ and NADPH are typically the active forms (outside of oxidative phosphorylation). NAD+ participates in oxidative (and usually catabolic) reactions, while NADPH participates in reductive (and usually anabolic) reactions.
The Macrobian ruler, who was elected based on his stature and beauty, replied instead with a challenge for his Persian counterpart in the form of an unstrung bow: if the Persians could manage to draw it, they would have the right to invade his country; but until then, they should thank the gods that the Macrobians never decided to invade their empire. The Macrobians were a regional power reputed for their advanced architecture and gold wealth, which was so plentiful that they shackled their prisoners in golden chains. During the classical period, the Barbara city-states of Mosylon, Opone, Mundus, Isis, Malao, Avalites, Essina, Nikon and Sarapion developed a lucrative trade network, connecting with merchants from Ptolemaic Egypt, Ancient Greece, Phoenicia, Parthian Persia, Saba, the Nabataean Kingdom, and the Roman Empire. They used the ancient Somali maritime vessel known as the beden to transport their cargo.
== Psychoactive use == In Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs, Freye asserts, "Few substances have received as many severely negative recreational experience reports as has Datura." The overwhelming majority of those who describe their use of Datura find their experiences extremely unpleasant—both mentally and often physically. However, anthropologists have found that indigenous groups, with a great deal of experience and detailed knowledge of Datura, have been known to use Datura spiritually (including the Navajo and especially the Havasupai). Adequate knowledge of Datura's properties is necessary to facilitate a safe experience. The ancient inhabitants of what became central and southern California used to ingest Datura to "commune with deities through visions". The Southern Paiute believe Datura can help locate missing objects. In ancient Mexico, Datura also played an important role in the religion of the Aztecs and the practices of their medicine men and necromancers. It was reportedly used by the Aztecs for ritual sacrifice and malevolent purposes as well. In modern-day Mexico, some Datura species are still used for sorcery and other occult practices, mostly in the southern region of Veracruz, specifically in the city of Catemaco. In Afghanistan, it was used by the Malang as a shamanic initiation rite and to contact the "other-world". Bernardino de Sahagún, in around 1569, called attention to Datura in these words: "It is administered in potions in order to cause harm to those who are objects of hatred.
Sources: en.wikipedia.org
=== Sultanate and Kingdom of Egypt (1915–1953) === Brigadier Peter Acland (4th class), 1936 Sir Pratap Singh of Idar (Grand Cordon), 1918 Judge Sir Maurice Amos (Grand Cordon) Maharaja Jagatjit Singh Bahadur of Kapurthala (Grand Cordon), 1924 Major Henry Beaumont (4th Class), 1916 Rear Admiral Richard Bevan (4th Class), 1919 Field Marshall Lord Birdwood Lieutenant General Louis Bols Lieutenant Colonel Arthur Borton VC, DSO (3rd Class) Howard Carter, British archaeologist and Egyptologist (3rd Class), 1926 Jovan Dučić Major Aubrey Faulkner Major General Harold Franklyn, Commandant Sudan Defence Force, 1939 Major Harry Gardner (4th Class), 1922 Lieutenant Colonel Alexander Kearsey (3rd Class) Harold Knox-Shaw, British astronomer Lancelot Lowther, 6th Earl of Lonsdale, 1920 Naguib Pasha Mahfouz, obstetrician and gynecologist, 1919 Lieutenant Colonel Cecil L'Estrange Malone David McAllister, Engineer-in-Chief, Egyptian State Railways, (3rd Class), 1916 Earl Mountbatten of Burma, (fourth class), 1922 Charles Paget, 6th Marquess of Anglesey, 1915 General Sir William Peyton (2nd Class), 1916 General Hussein Refki Pasha (Grand Cordon) Admiral of the Fleet The Earl of Cork and Orerry, 3rd class (1916) Admiral Francis Mitchell (Royal Navy officer) Rear Admiral Eric Gascoigne Robinson Captain George Francis Scott Elliot Dr. Hassan Omar Shaheen – Professor of ENT Kasr El-Aini Hospital, Cairo. Circa 1920 Major-General Sir Charlton Watson Spinks, last Sirdar of Egypt (Grand Cordon), 1931 Dr.
=== Regeneration === Methionine can be regenerated from homocysteine via (4) methionine synthase in a reaction that requires vitamin B12 as a cofactor. Homocysteine can also be remethylated using glycine betaine (N,N,N-trimethylglycine, TMG) to methionine via the enzyme betaine-homocysteine methyltransferase (E.C.2.1.1.5, BHMT). BHMT makes up to 1.5% of all the soluble protein of the liver, and recent evidence suggests that it may have a greater influence on methionine and homocysteine homeostasis than methionine synthase.
=== Discovery of catalytic RNA (ribozymes) === An experimental system was developed in which an intron-containing rRNA precursor from the nucleus of the ciliated protozoan Tetrahymena could be spliced in vitro. Subsequent biochemical analysis shows that this group I intron was self-splicing; that is, the precursor RNA is capable of carrying out the complete splicing reaction in the absence of proteins. In separate work, the RNA component of the bacterial enzyme ribonuclease P (a ribonucleoprotein complex) was shown to catalyze its tRNA-processing reaction in the absence of proteins. These experiments represented landmarks in RNA biology, since they revealed that RNA could play an active role in cellular processes, by catalyzing specific biochemical reactions. Before these discoveries, it was believed that biological catalysis was solely the realm of protein enzymes.
Sources: en.wikipedia.org
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.
It is shorter than the native hormone and carries a cyclic constraint that improves stability. These changes raise receptor potency and slow breakdown relative to the naturally occurring peptide.
Published accounts date its development to the 1980s, when researchers were generating analogues of melanocyte-stimulating hormone. That work aimed to produce more stable compounds for studying pigmentation biology.
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.