Melanotan II, usually shortened to MT-2, is a small cyclic peptide derived from α-melanocyte-stimulating hormone (α-MSH). It keeps the hormone’s receptor-binding core but folds it into a ring, and it activates four of the five melanocortin receptors. That broad activity made it one of the most widely used pharmacological tools in melanocortin neuroscience, from feeding circuits in the hypothalamus to autonomic reflexes.
It also has a complicated public profile, because unlicensed products sold under the melanotan name have drawn repeated warnings from health agencies. This overview sticks to the science: where the molecule came from, how it interacts with melanocortin receptors, the animal and chemical research built on it, and what that research does not establish.
At a glance
- Class: Synthetic cyclic heptapeptide; non-selective melanocortin receptor agonist
- Origin: Cyclic lactam α-melanotropin program at the University of Arizona, late 1980s (Al-Obeidi et al., 1989)
- Structure: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2; C50H69N15O9; 1024.2 g/mol; CAS 121062-08-6
- Main research areas: melanocortin receptor pharmacology, central MC3R/MC4R signaling, rodent models of erectile physiology, peptide synthesis methods
- Regulatory status: Not approved by the FDA or any other regulator
Structure and origin
Natural α-MSH is a linear 13-residue peptide that proteases break down within minutes. The first major improvement came in 1980, when Sawyer and colleagues introduced two substitutions, norleucine at position 4 and D-phenylalanine at position 7, producing the long-acting linear analog later called melanotan I (Sawyer et al., 1980). The same Arizona chemistry and pharmacology groups then asked whether the essential portion of the hormone could be made even smaller and more rigid.
Al-Obeidi and colleagues used molecular dynamics modeling to design cyclic analogs in which a lactam bond between the side chains of aspartic acid and lysine closes a ring around the His-D-Phe-Arg-Trp core (Al-Obeidi et al., 1989). The best of these became MT-2: seven residues, an acetylated norleucine at the N-terminus, and an amidated C-terminus. Compared with α-MSH, the molecule is about half the length, resists enzymatic degradation, and holds the core residues in a conformation that suits several receptor subtypes.
MT-2 is closely related to bremelanotide (PT-141), which shares the same ring and N-terminal residues but ends in a free carboxylic acid rather than an amide. The two compounds have separate CAS numbers and separate regulatory histories. Synthesis remains an active topic: most MT-2 is made by solid-phase methods, and Ryakhovsky and colleagues described the first preparative route in solution, an approach suited to larger scales (Ryakhovsky et al., 2008).
Mechanism: what the research shows
The melanocortin system has five G protein-coupled receptors. MC2R responds only to adrenocorticotropic hormone; MC1R, MC3R, MC4R and MC5R respond to MSH peptides and signal mainly through Gs and cAMP. In receptor assays, MT-2 activates all four of the MSH-responsive subtypes, so it is a broad agonist rather than a selective probe. Its value lies in its potency and stability, which allow researchers to switch on melanocortin signaling and then use selective antagonists or knockout animals to work out which receptor is responsible.
Central effects are tied mainly to MC3R and MC4R, which are expressed in the hypothalamus, brainstem and spinal cord. In peripheral tissues, MC1R on melanocytes and MC5R in exocrine glands account for other responses studied in cell systems. Hadley and Dorr’s historical review traces how this receptor profile shaped the compound’s development and its use as a research tool (Hadley and Dorr, 2006).
Key areas of study
Central melanocortin signaling and energy balance
MT-2 has been a standard agonist in rodent studies of hypothalamic circuits that regulate food intake. Typical designs give the peptide centrally, measure intake or energy expenditure, and test whether an MC3R/MC4R antagonist or receptor deletion blocks the response. The Arizona program’s review summarizes how MT-2 entered this line of work (Hadley and Dorr, 2006).
Erectile and autonomic physiology
In rats and other models, melanocortin agonists including MT-2 have been used to study spinal and supraspinal pathways controlling penile erection, with nitric oxide signaling as a downstream readout. King and colleagues reviewed receptor subtypes, sites of action and the peptides used in this research (King et al., 2007).
Peripheral MC1R biology in cell systems
Melanocyte and melanoma cell lines express MC1R and are used for binding and cAMP assays with MT-2 and related analogs, alongside native α-MSH and the linear analog melanotan I (Sawyer et al., 1980; Hadley and Dorr, 2006).
Peptide chemistry
As a compact, cyclic, well-characterized peptide, MT-2 serves as a test scaffold for synthesis and cyclization methods, from the original lactam design (Al-Obeidi et al., 1989) to solution-phase manufacturing routes (Ryakhovsky et al., 2008).
What the evidence does not show
- The mechanistic and physiological data come from receptor assays, cell lines and animal models. They do not establish effects or safety in humans.
- Because MT-2 activates several receptor subtypes at once, attributing any single response to one receptor requires antagonists, knockouts or more selective compounds.
- Early clinical evaluations did not lead to an approved product, and dermatology commentators have raised concerns about unregulated melanotan products circulating outside research settings (Langan et al., 2010).
- Results for bremelanotide or melanotan I cannot be assumed to apply to MT-2, or the reverse.
Regulatory status
Melanotan II is not approved by the FDA or by any other drug regulator. Health agencies in several countries have issued warnings about unlicensed melanotan products. Bremelanotide, a related peptide, is the active ingredient of a separate FDA-approved drug for a specific indication; MT-2 is not that product. Rogue Compounds sells MT-2 as a research reagent only.
Handling and storage in the lab
Lyophilized MT-2 should be kept sealed and refrigerated at 2–8°C (36–46°F), protected from light.
Sourcing and documentation
Rogue Compounds has MT-2 made in small batches. Every vial carries a batch number and a QR code that opens the independent U.S. testing lab’s own report for that batch, and the same batch COA is on the product page and in the COA Library.
View MT-2 (Melanotan II) on Rogue Compounds
References
- Sawyer TK, et al. 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Proc Natl Acad Sci U S A. 1980;77(10):5754-5758. PMID 6777774
- Al-Obeidi F, et al. Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics. J Med Chem. 1989;32(12):2555-2561. PMID 2555512
- Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006;27(4):921-930. PMID 16412534
- King SH, et al. Melanocortin receptors, melanotropic peptides and penile erection. Curr Top Med Chem. 2007;7(11):1098-1106. PMID 17584130
- Ryakhovsky VV, et al. The first preparative solution phase synthesis of melanotan II. Beilstein J Org Chem. 2008;4:39. PMID 19043625
- Langan EA, Nie Z, Rhodes LE. Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'? Br J Dermatol. 2010;163(3):451-455. PMID 20545686
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.