MT-1, or melanotan 1, is a 13-residue synthetic analog of α-melanocyte-stimulating hormone (α-MSH) with two amino acid substitutions that make it far more stable and potent than the natural hormone. Its chemical name, [Nle4, D-Phe7]-α-MSH, describes those changes, and its nonproprietary drug name is afamelanotide.
For researchers, MT-1 is a high-potency agonist used above all to study the melanocortin-1 receptor (MC1R), and it is a historical reference point for an entire family of melanocortin peptides. This overview covers how it was designed, its receptor pharmacology, the model systems where it is used, its regulatory history, and the limits of what preclinical data show. The material discussed here is a research reagent, which is distinct from any approved drug product.
At a glance
- Class: Synthetic linear 13-amino-acid peptide; α-MSH analog and melanocortin receptor agonist
- Origin: Reported in 1980 by Sawyer, Hruby, Hadley and colleagues at the University of Arizona (Sawyer et al., 1980)
- Structure: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2; C78H111N21O19; 1646.8 g/mol; CAS 75921-69-6
- Main research areas: MC1R pharmacology, melanocyte and melanoma cell biology, melanocortin structure–activity work, analytical chemistry
- Regulatory status: Afamelanotide is the active ingredient of an FDA-approved implant for a specific indication (2019); the lyophilized material sold here is a research reagent
Structure and origin
α-MSH is cut from the precursor pro-opiomelanocortin and acts on several melanocortin receptors. As a research tool it has two weaknesses: methionine at position 4 oxidizes easily, and the peptide is degraded quickly by proteases. Sawyer and colleagues addressed both. Replacing methionine with norleucine, an unbranched analog without sulfur, removed the oxidation site. Replacing L-phenylalanine at position 7 with its D-isomer altered the backbone around the His-Phe-Arg-Trp core, the sequence that contacts the receptor.
In the original bioassays, the doubly substituted peptide was markedly more potent than α-MSH and its activity lasted far longer, which the authors described in the paper’s title as “ultralong biological activity” (Sawyer et al., 1980). The D-Phe7 change in particular proved important across the field: it reappears in the cyclic analogs that followed, including the lactam-bridged compounds that led to melanotan II (Al-Obeidi et al., 1989). MT-1 keeps the full 13-residue length of the hormone, with an acetylated N-terminus and an amidated C-terminus, so it is a linear molecule rather than a ring.
Mechanism: what the research shows
MT-1 binds the melanocortin receptors that respond to MSH peptides, with especially high potency at MC1R. MC1R is a Gs-coupled receptor; activation raises intracellular cAMP, which in melanocytes drives expression and activity of enzymes in the eumelanin synthesis pathway, including tyrosinase. In cell systems, this receptor-to-cAMP-to-enzyme chain is the main readout for MT-1 activity.
Hadley and Dorr’s review describes how the Arizona group moved from receptor assays and animal bioassays to formal development of the compound, and how its longer duration of action compared with α-MSH shaped that program (Hadley and Dorr, 2006). Beyond pigment cells, MC1R is expressed on some immune and endothelial cells, and reviews of melanotropic peptides discuss MC1R signaling in those cell types as a separate research thread (Langan et al., 2010).
Key areas of study
Receptor pharmacology
MT-1 is used in radioligand binding and cAMP assays alongside native α-MSH, cyclic analogs and antagonists. Comparing linear and cyclic ligands across MC1R, MC3R, MC4R and MC5R helped define which structural features drive potency and selectivity (Sawyer et al., 1980; Al-Obeidi et al., 1989).
Melanocyte and melanoma cell biology
Cultured melanocytes and melanoma cell lines are the standard in-vitro systems. Endpoints include cAMP accumulation, tyrosinase activity, eumelanin content and downstream gene expression. These experiments describe receptor signaling in cells and do not predict outcomes in people (Hadley and Dorr, 2006).
Structure–activity history
Because it was one of the first highly potent α-MSH analogs, MT-1 is a standard comparator in papers on newer melanocortin ligands. The design principles it demonstrated, especially D-Phe at position 7, carried directly into the cyclic analogs (Al-Obeidi et al., 1989).
Clinical and regulatory history
As afamelanotide, the compound was developed into a long-acting implant and evaluated in clinical studies for a rare photosensitivity disorder, erythropoietic protoporphyria. A 2021 review summarizes that development history and regulatory path (Wensink et al., 2021). The implant formulation and its approval are specific to that product and that indication.
What the evidence does not show
- Receptor and cell-culture findings describe signaling in model systems. They do not establish any effect of research-grade MT-1 in humans.
- The approved product is a specific controlled-release implant used under medical supervision for one condition. That approval does not extend to lyophilized research material or to any other use.
- MT-1 acts on more than one melanocortin receptor; MC1R-specific conclusions require appropriate controls.
- Dermatology authors have raised concerns about unlicensed melanotan products sold outside regulated channels (Langan et al., 2010).
Regulatory status
Afamelanotide is the active ingredient of Scenesse, a subcutaneous implant approved by the FDA in October 2019 for a specific indication, the prevention of phototoxicity in adults with erythropoietic protoporphyria; it is also authorized in the European Union. The lyophilized MT-1 sold by Rogue Compounds is a research reagent, not Scenesse or any other approved drug product, and it is not for human use. Health agencies in several countries have warned about unlicensed melanotan products.
Handling and storage in the lab
Lyophilized MT-1 should be kept sealed and refrigerated at 2–8°C (36–46°F), protected from light.
Sourcing and documentation
Rogue Compounds has MT-1 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-1 (Melanotan 1) 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
- 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
- Wensink D, Wagenmakers MAEM, Langendonk JG. Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria. Expert Rev Clin Pharmacol. 2021;14(2):151-160. PMID 33507118
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.