If you have been reading about alpha-MSH and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Updated 2025-08-09. Numbers and descriptions here follow the published literature rather than marketing material.
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.
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 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.
| 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 |
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.
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.
In 2018, the DeepMind Safety team outlined AI safety problems in specification, robustness, and assurance. The following year, researchers organized a workshop at ICLR that focused on these problem areas. In 2021, Unsolved Problems in ML Safety was published, outlining research directions in robustness, monitoring, alignment, and systemic safety. In 2023, Rishi Sunak said he wants the United Kingdom to be the "geographical home of global AI safety regulation" and to host the first global summit on AI safety. The AI safety summit took place in November 2023, and focused on the risks of misuse and loss of control associated with frontier AI models. During the summit, the intention to create the International Scientific Report on the Safety of Advanced AI was announced. In 2024, The US and UK forged a new partnership on the science of AI safety. The MoU was signed on 1 April 2024 by US commerce secretary Gina Raimondo and UK technology secretary Michelle Donelan to jointly develop advanced AI model testing, following commitments announced at an AI Safety Summit in Bletchley Park in November. In 2025, an international team of 96 experts chaired by Yoshua Bengio published the first International AI Safety Report. The report, commissioned by 30 nations and the United Nations, represents the first global scientific review of potential risks associated with advanced artificial intelligence.
In August 2020, it was announced that Jensen Ackles would be joining the show as Soldier Boy, promising that "the character would bring so much humor, pathos, and danger to the role." Laura Jean Shannon designed the suit for the character using military green and referring to him as "the original bad-ass". She eventually explained how the suit fits his character: "Our goal was to highlight a bygone era of overt masculinity and grit. With that pedigree we dove headfirst into baking in an all-American quality grounded in a military soldier's practicality with a heavy dose of old school cowboy swagger. We knew that the actor had to have Steve McQueen looks and chops with a John Wayne attitude — luckily Jensen Ackles embodies all of that." In October 2020, it was announced that Claudia Doumit and Colby Minifie would reprise their roles as Victoria Neuman and Ashley Barrett respectively, with both being promoted to series regulars. In March 2021, it was announced that Katia Winter was cast as the Russian mob boss Little Nina. That June, Miles Gaston Villanueva, Sean Patrick Flannery, Nick Wechsler and Laurie Holden were cast as Supersonic, Gunpowder, Blue Hawk, and Crimson Countess respectively. In October 5, Jack Doolan, Kristin Booth, and Frances Turner joined the series with Booth and Dooland appearing as the TNT Twins with the former being Tessa TNT and the latter being Tommy TNT, while Turner replaces Alvina August as MM's ex-wife Monique.
== History == Vitamin A toxicity is known to be an ancient phenomenon; fossilized skeletal remains of early humans suggest bone abnormalities may have been caused by hypervitaminosis A, as observed in a fossilised leg bone of an individual of Homo erectus, which bears abnormalities similar to those observed in people suffering from an overdose of Vitamin A in the present day. Vitamin A toxicity has long been known to the Inuit, as they will not eat the liver of polar bears or bearded seals due to them containing dangerous amounts of Vitamin A. It has been known to Europeans since at least 1597 when Gerrit de Veer wrote in his diary that, while taking refuge in the winter in Nova Zemlya, he and his men became severely ill after eating polar bear liver. It is claimed that, in 1913, Antarctic explorers Douglas Mawson and Xavier Mertz were both poisoned (and Mertz died) from eating the livers of their sled dogs during the Far Eastern Party. Another study suggests, however, that exhaustion and diet change are more likely to have caused the tragedy.
For comparison, the rate in the general population has been found to be 1.0–1.8 per 1000 person-years, and the rate in premenopausal women taking birth control pills has been found to be 3.5 per 1000 patient-years. There was significant heterogeneity in the rates of VTE across the included studied, and the meta-analysis was unable to perform subgroup analyses between estrogen type, estrogen route, estrogen dosage, concomitant antiandrogen or progestogen use, or patient characteristics (e.g., sex, age, smoking status, weight) corresponding to known risk factors for VTE. Due to the inclusion of some studies using ethinylestradiol, which is more thrombotic and is no longer used in transgender women, the researchers noted that the VTE risk found in their study may be an overestimate. In a 2016 study that specifically assessed oral estradiol, the incidence of VTE in 676 transgender women who were treated for an average of 1.9 years each was one individual, or 0.15% of the group, with an incidence of 7.8 events per 10,000 person-years. The dosage of oral estradiol used was 2 to 8 mg/day. Almost all of the transgender women were also taking spironolactone (94%), a subset were also taking finasteride (17%), and fewer than 5% were also taking a progestogen (usually oral progesterone). The findings of this study suggest that the incidence of VTE is low in transgender women taking oral estradiol. Cardiovascular health in transgender women has been reviewed in recent publications.
Sources: en.wikipedia.org
There is significant controversy about the level of risk of stroke from neck manipulation. It may be that manipulation can cause dissection, or it may be that the dissection is already present in some people who seek manipulative treatment. At this time, conclusive evidence does not exist to support either a strong association between neck manipulation and stroke, or no association. However, the two most authoritative articles on the subject, recent literature reviews and analyses, conclude that although there exists an association between stroke from vertebral artery dissection and chiropractic adjustment, there is insufficient evidence to indicate that the adjustment caused the dissection. A recent meta-analysis of the published data on the topic also looked to apply Hill's criteria for assigning causation in biological systems to the relationship between chiropractic adjustment and cervical artery dissection, finding that the relationship did not fulfill the required criteria for causality.
=== Strategies for toxicity prevention === Understanding the mechanisms behind the toxicity of gliotoxin can open new possibilities for the use of gliotoxin therapeutically or as a diagnostic test for some conditions. One potential strategy that has been explored to reduce the toxicity of the fungi that produce gliotoxin is to target the gli gene cluster that controls the expression of gliotoxin protein. The disulfide bridge of gliotoxin is crucial to its toxicity, so it is theorized that the tailoring of enzymes to prevent the disulfide bridge closure by interfering with GliT or by catalyzing another reaction to block the sulfur residues may be beneficial in reducing the toxicity of those fungi. Another potential strategy is the targeting of the transcriptional activator GliZ, as deletion of the GliZ resulted in abrogated gliotoxin biosynthesis. This leads to the possible targeting of GliZ itself rather than any gene-based methodology to prevent it from binding to the gli gene cluster and activate transcription of the genes required for gliotoxin biosynthesis. One possible strategy for disrupting the regulation of gliotoxin transport is depleting the amount of GipA in the cell. GipA is a transcriptional regulator for the expression of the GliA transporter protein, which is required for gliotoxin secretion. These biosynthetic strategies for reducing the toxicity of pathogenic fungal strains that produce gliotoxin are still in their early stages of exploration but could provide novel methodologies for the adoption of therapeutic uses for gliotoxin.
=== Emerald Twilight and beyond === In Emerald Twilight, Hal Jordan is driven to insanity and becomes the villain Parallax following the destruction of his hometown Coast City. He attacks Boodikka, cuts off her right hand, and takes her power ring, leaving her for dead. Boodikka is later revealed to have survived, but has been placed in suspended animation by the Manhunters along with many other former Green Lanterns, with the Manhunters intending to harness their energy to create more advanced Manhunters. After being freed, Boodikka is shocked that she no longer has her hand, and appears to remember nothing past her encounter with Parallax. During a later confrontation with the Manhunters, Kreon is killed and his ring chooses Boodikka. She resumes her duties in the Green Lantern Corps, replacing her lost hand with a Lantern construct.
Males perform a sequence of five behavioral patterns to court females. First, males orient themselves while playing a courtship song by horizontally extending and vibrating their wings. Soon after, the male positions himself at the rear of the female's abdomen in a low posture to tap and lick the female genitalia. Finally, the male curls his abdomen and attempts copulation. Females can reject males by moving away, kicking, and extruding their ovipositor. Copulation lasts around 15–20 minutes, during which males transfer a few hundred, very long (1.76 mm) sperm cells in seminal fluid to the female. Females store the sperm in a tubular receptacle and in two mushroom-shaped spermathecae; sperm from multiple matings compete for fertilization. A last male precedence is believed to exist; the last male to mate with a female sires about 80% of her offspring. This precedence was found to occur through both displacement and incapacitation. The displacement is attributed to sperm handling by the female fly as multiple matings are conducted and is most significant during the first 1–2 days after copulation. Displacement from the seminal receptacle is more significant than displacement from the spermathecae. Incapacitation of first male sperm by second male sperm becomes significant 2–7 days after copulation. The seminal fluid of the second male is believed to be responsible for this incapacitation mechanism (without removal of first male sperm) which takes effect before fertilization occurs.
Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC). It is available as a generic medication.
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.
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.