A practical reference on alpha-MSH analogue: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-02-03. Anything still debated is marked as such rather than presented as settled.
Melanotan-2 is a synthetic cyclic heptapeptide designed as an analogue of alpha-melanocyte-stimulating hormone. Its sequence incorporates a lactam bridge that constrains the peptide into a ring, which increases resistance to enzymatic breakdown relative to the natural hormone. Researchers at the University of Arizona synthesised the compound in the late 1980s and early 1990s while studying pigmentation pathways. It has never received marketing approval from any national medicines regulator. In the scientific literature it is usually described as a laboratory research reagent rather than a therapeutic product.
The peptide acts as a non-selective agonist at melanocortin receptors, showing affinity for MC1R, MC3R, MC4R and MC5R. Activation of MC1R on melanocytes drives the conversion of tyrosine into melanin and shifts production toward the darker eumelanin form. MC4R signalling in the central nervous system is linked to appetite and energy balance, which helps explain why reduced food intake appeared in early human studies. Effects on MC4R and on vascular tone also account for the erectile responses recorded as unexpected findings in those same trials.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Chemical class | Synthetic cyclic heptapeptide | Alpha-MSH analogue with a lactam ring |
| Molecular formula | C50H69N15O9 | Commonly cited value for the neutral peptide |
| Molecular weight | 1024.18 g/mol | Calculated for the free molecule |
| Appearance | White to off-white powder | Typically supplied as a lyophilised solid |
| Solubility | Soluble in water, DMSO and ethanol | Dissolution in pure water is often slow |
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.
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.
Mutarotation consists of a temporary reversal of the ring-forming reaction, resulting in the open-chain form, followed by a reforming of the ring. The ring closure step may use a different −OH group than the one recreated by the opening step (thus switching between pyranose and furanose forms), or the new hemiacetal group created on C-1 may have the same or opposite handedness as the original one (thus switching between the α and β forms). Thus, though the open-chain form is barely detectable in solution, it is an essential component of the equilibrium. The open-chain form is thermodynamically unstable, and it spontaneously isomerizes to the cyclic forms. (Although the ring closure reaction could in theory create four- or three-atom rings, these would be highly strained, and are not observed in practice.) In solutions at room temperature, the four cyclic isomers interconvert over a time scale of hours, in a process called mutarotation. Starting from any proportions, the mixture converges to a stable ratio of α:β 36:64. The ratio would be α:β 11:89 if it were not for the influence of the anomeric effect. Mutarotation is considerably slower at temperatures close to 0 °C (32 °F).
As such, the transdermal route cannot easily achieve adequate circulating progesterone levels, and this makes transdermal progesterone impractical for systemic therapy. Clinical studies have found only very low circulating levels of progesterone with the use of transdermal progesterone, and these levels are thought to be insufficient to confer endometrial protection against estrogens. The range of circulating levels of progesterone that has been observed in clinical studies with various formulations and doses of transdermal progesterone is 0.38 to 3.5 ng/mL. Although very low levels of progesterone have been observed in venous blood with transdermal progesterone, very high and in fact greatly supraphysiological levels of progesterone have unexpectedly been found in saliva and capillary blood. In one study, the levels of progesterone in saliva and capillary blood were 10- and 100-fold greater than levels in venous blood, respectively. Levels of salivary progesterone that have been observed have ranged from 2.9 to 2,840 ng/mL. The high salivary and capillary blood levels of progesterone suggest that despite low circulating levels of progesterone, systemic distribution of progesterone and considerable exposure of some tissues to the hormone may be occurring with transdermal progesterone somehow. However, the few clinical studies that have assessed the effects of transdermal progesterone on the endometrium have had mixed findings, and further research is needed to determine whether it can confer adequate endometrial protection as a component of menopausal hormone therapy.
There is an increased possibility of protein deficiency with a strictly vegetable diet, unless the vegetable sources are carefully combined so that they complement one another. In 1985, the principle of protein combining was explained by J. Rigó:
Bryant Park was initially supposed to reopen in late 1990 or early 1991. The reopening date was pushed back due to delays caused by the construction of the library's stacks. In June 1991, the city and BPRC reached an agreement to reopen the western section of Bryant Park on summer weekdays. The park was soft reopened on April 21, 1992, with the official reopening set for nearly a month later. The new design received widespread acclaim. Deemed "a triumph for many" by New York Times architectural critic Paul Goldberger, the renovation was lauded not only for its architectural excellence, but also for adhering to Whyte's vision. According to Goldberger, Biederman "understood that the problem of Bryant Park was its perception as an enclosure cut off from the city; he knew that, paradoxically, people feel safer when not cut off from the city, and that they feel safer in the kind of public space they think they have some control over." The renovation was lauded as "The Best Example of Urban Renewal" by New York magazine, and was described by Time as a "small miracle". Many awards followed, including a Design Merit Award from Landscape Architecture Magazine, and the 1996 Award for Excellence from the Urban Land Institute (ULI). The park has been extolled for its relative calmness and cleanness. Through the 21st century, Bryant Park remained a model of civic renewal that mayors of other cities, such as Jorge Elorza of Providence, Rhode Island, sometimes held up as a model to emulate. Bryant Park was described in the media as an example of New York City's 1990s revival.
Sources: en.wikipedia.org
The fungus is highly toxic, and is responsible for the majority of fatal mushroom poisonings worldwide. Its biochemistry has been researched intensively for decades, and 30 grams (1.1 ounces), or half a cap, of this mushroom is estimated to be enough to kill a human. On average, one person dies a year in North America from death cap ingestion. The toxins of the death cap mushrooms primarily target the liver, but other organs, such as the kidneys, are also affected. Symptoms of death cap mushroom toxicity usually occur 6 to 12 hours after ingestion. Symptoms of ingestion of the death cap mushroom may include nausea and vomiting, which is then followed by jaundice, seizures, and coma, which will lead to death. The mortality rate of ingestion of the death cap mushroom is believed to be around 10–30%. Some authorities strongly advise against putting suspected death caps in the same basket with fungi collected for the table and to avoid even touching them. Furthermore, the toxicity is not reduced by cooking, freezing, or drying. Poisoning incidents usually result from errors in identification. Recent cases highlight the issue of the similarity of A. phalloides to the edible paddy straw mushroom (Volvariella volvacea), with East and Southeast Asian immigrants in Australia and the West Coast of the U.S. falling victim. In an episode in Oregon, four members of a Korean family required liver transplants. Many North American incidents of death cap poisoning have occurred among Laotian and Hmong immigrants, since it is easily confused with A.
March 4–5 – The Senate and House of Representatives reject War Powers Resolutions to halt Trump's actions in the 2026 Iran War without congressional approval. March 5–17 – The 2026 World Baseball Classic is held in the United States, including Puerto Rico, as well as in Japan. The championship game is held at LoanDepot Park in Miami.
Possibly the most common use of affinity chromatography is for the purification of recombinant proteins. Proteins with a known affinity are protein tagged in order to aid their purification. The protein may have been genetically modified so as to allow it to be selected for affinity binding; this is known as a fusion protein. Protein tags include hexahistidine (His), glutathione-S-transferase (GST), maltose binding protein (MBP), and the Colicin E7 variant CL7 tag. Histidine tags have an affinity for nickel, cobalt, zinc, copper and iron ions which have been immobilized by forming coordinate covalent bonds with a chelator incorporated in the stationary phase. For elution, an excess amount of a compound able to act as a metal ion ligand, such as imidazole, is used. GST has an affinity for glutathione which is commercially available immobilized as glutathione agarose. During elution, excess glutathione is used to displace the tagged protein. CL7 has an affinity and specificity for Immunity Protein 7 (Im7) which is commercially available immobilized as Im7 agarose resin. For elution, an active and site-specific protease is applied to the Im7 resin to release the tag-free protein.
Among the actinides, thorium and uranium are the easiest to isolate. Thorium is extracted mostly from monazite: thorium pyrophosphate (ThP2O7) is reacted with nitric acid, and the produced thorium nitrate treated with tributyl phosphate. Rare-earth impurities are separated by increasing the pH in sulfate solution. In another extraction method, monazite is decomposed with a 45% aqueous solution of sodium hydroxide at 140 °C. Mixed metal hydroxides are extracted first, filtered at 80 °C, washed with water and dissolved with concentrated hydrochloric acid. Next, the acidic solution is neutralized with hydroxides to pH = 5.8 that results in precipitation of thorium hydroxide (Th(OH)4) contaminated with ~3% of rare-earth hydroxides; the rest of rare-earth hydroxides remains in solution. Thorium hydroxide is dissolved in an inorganic acid and then purified from the rare earth elements. An efficient method is the dissolution of thorium hydroxide in nitric acid, because the resulting solution can be purified by extraction with organic solvents:
At least several thousand years ago, some humans developed a mutation in the MCM6 gene that keeps the LCT gene turned on even after breast feeding is stopped. Populations that are lactose intolerant lack this mutation. The LCT and MCM6 genes are both located on the long arm (q) of chromosome 2 in region 21. The locus can be expressed as 2q21. The lactase deficiency also could be linked to certain heritages and varies widely. A 2016 study of over 60,000 participants from 89 countries found regional prevalence of lactose malabsorption was "64% (54–74) in Asia (except Middle East), 47% (33–61) in eastern Europe, Russia, and former Soviet Republics, 38% (CI 18–57) in Latin America, 70% (57–83) in the Middle East, 66% (45–88) in northern Africa, 42% (13–71) in northern America, 45% (19–71) in Oceania, 63% (54–72) in sub-Saharan Africa, and 28% (19–37) in northern, southern and western Europe." According to Johns Hopkins Medicine, in the United States lactose intolerance is more common in Asian Americans, African Americans, Mexican Americans, and Native Americans. Analysis of the DNA of 94 ancient skeletons in Europe and Russia concluded that the mutation for lactose tolerance appeared about 4,300 years ago and spread throughout the European population. Some human populations have developed lactase persistence, in which lactase production continues into adulthood probably as a response to the benefits of being able to digest milk from farm animals.
Sources: en.wikipedia.org
Evidence from the study of the organization of mineral nanocrystals in teeth of extant and extinct hominins and other primates, indicating that enamel nanocrystal misorientation in hominin teeth changed in conjunction with dietary shifts of members of the human lineage (including the introduction of meat and agricultural products into their diet), is presented by Gilbert et al. (2026). Gat, Subsol & Braga (2026) compare the development of the cortical bone in the mandible during the early ontogeny of extant chimpanzees and humans and in fossil hominins, linking the robust morphology of the mandible of Paranthropus to a distinct developmental trajectory. Orr et al. (2026) provide a catalog of isolated postcranial remains of hominins from Drimolen (South Africa) collected between 1994 and 2015. New postcranial fossil material of hominins is reported from the Kromdraai fossil site (South Africa) by DeSilva et al. (2026). Alemseged et al. (2026) report the discovery of fossil material of Paranthropus from the Mille-Logya research area determined to be between 2.5 and 2.9-million-years-old, representing the first record of the genus in the Afar region of Ethiopia and one of the oldest records of a member of the genus reported to date. Rak & Kimbel (2026) interpret the prognathism observed in the specimen KNM WT 17000 as a derived rather than primitive trait, and interpret Australopithecus/Paranthropus aethiopicus as the probable sister taxon of Australopithecus/Paranthropus boisei. Critical reevaluation of the study of Zanolli et al.
==== Suicides and homicides ==== Tyson Mathews (1983–2013) died in Teralba, New South Wales, Australia, on 7 November 2013 just six days after his 30th birthday. The cause of death was determined to be suicide by hanging. At the time of his death, he was subject to a community treatment order (CTO) mandating depot antipsychotic injections of paliperidone palmitate (brand name Invega Sustenna). The inquest specifically investigated whether this medication was a contributing factor. His mother was concerned about the appropriateness of paliperidone palmitate. She observed that after the dose was increased, her son's psychotic symptoms settled, but he became "markedly more depressed." She questioned whether the drug contributed to his condition and death. Despite his depression (neuroleptic dysphoria) worsening, Ms. Mathews felt healthcare professionals did not fully acknowledge the deterioration. Andrew Jeffrey Rich (1989–2019) was a Wisconsin man placed under court-ordered assisted outpatient treatment (AOT) following a breakdown in May 2017. He was required to receive regular injections of Invega Sustenna under Wisconsin's Chapter 51 commitment law. Over approximately 18 months, recommitment orders were repeatedly extended on the basis that he denied having a mental illness and would likely stop medication if released, despite his psychiatrist acknowledging no observed psychotic symptoms during that period and Rich living and working independently in the community.
One measure of how well a molecule fits a receptor is its binding affinity, which is inversely related to the dissociation constant Kd. A good fit corresponds with high affinity and low Kd. The final biological response (e.g. second messenger cascade, muscle-contraction), is only achieved after a significant number of receptors are activated. Affinity is a measure of the tendency of a ligand to bind to its receptor. Efficacy is the measure of the bound ligand to activate its receptor.
Although it is a relatively immature area of research, it appears that heterotrimeric G-proteins may also take part in non-GPCR signaling. There is evidence for roles as signal transducers in nearly all other types of receptor-mediated signaling, including integrins, receptor tyrosine kinases (RTKs), cytokine receptors (JAK/STATs), as well as modulation of various other "accessory" proteins such as GEFs, guanine-nucleotide dissociation inhibitors (GDIs) and protein phosphatases. There may even be specific proteins of these classes whose primary function is as part of GPCR-independent pathways, termed activators of G-protein signalling (AGS). Both the ubiquity of these interactions and the importance of Gα vs. Gβγ subunits to these processes are still unclear. There are two principal signal transduction pathways involving the G protein-linked receptors: the cAMP signal pathway and the phosphatidylinositol signal pathway.
Prior to founding the Center for Biomedical Mass Spectrometry at Boston University School of Medicine in 1994, Costello was a senior research scientist and the associate director of the National Institutes of Health Research Resource for Mass Spectrometry at Massachusetts Institute of Technology for 20 years. She is a William Fairfield Warren Distinguished Professor and the director of the Center for Biomedical Mass Spectrometry at the Boston University School of Medicine. Costello served as the president of the American Society for Mass Spectrometry (2002–2004), the Human Proteome Organization (2011–2012), and the International Mass Spectrometry Foundation (2014–2018). She currently serves on the board of directors of the US Human Proteome Organization, and the editorial board of Clinical Proteomics.
Sources: en.wikipedia.org
It is a synthetic cyclic heptapeptide modelled on alpha-melanocyte-stimulating hormone. A lactam bridge links two side chains, forming a ring that stabilises the molecule against proteolysis. It belongs to the broader melanocortin peptide family.
No national medicines agency has approved melanotan-2 for clinical use. Afamelanotide, a related but distinct peptide, holds a marketing authorisation in the European Union for a rare photosensitivity disorder. Melanotan-2 itself is handled as a laboratory chemical.
Its broad activity across melanocortin receptors makes it a tool for probing pigmentation, appetite and vascular signalling. Early trials recorded skin darkening and other effects that were not the original focus of the work. Those observations generated hypotheses that later studies have examined.
No. No major regulatory agency has granted a marketing authorisation for melanotan II as a medicine. Products sold under this name are generally presented as laboratory reagents and are not subject to the batch-release testing applied to approved drugs.