MT-1 (Melanotan 1) and MT-2 (Melanotan II) are both synthetic analogs of alpha-melanocyte-stimulating hormone (alpha-MSH), and both came out of the same University of Arizona research program. The key difference is shape. MT-1 is a linear 13-residue peptide that is most potent at the melanocortin-1 receptor. MT-2 is a compact seven-residue ring that activates four of the five melanocortin receptors. This guide compares them side by side and links to the full research overview for each.
All compounds discussed are sold for laboratory research use only. This page summarizes published research and is not guidance for human or veterinary use.
At a glance
| MT-1 (Melanotan 1) | MT-2 (Melanotan II) | |
|---|---|---|
| Shape | Linear peptide | Cyclic peptide (lactam bridge) |
| Size | 13 residues, 1646.8 g/mol | 7 residues, 1024.2 g/mol |
| Sequence | Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 | Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 |
| First reported | 1980 (Sawyer et al.) | Late 1980s (Al-Obeidi et al., 1989) |
| Receptor profile | Melanocortin agonist with especially high potency at MC1R | Broad agonist at MC1R, MC3R, MC4R and MC5R |
| Main research areas | MC1R pharmacology, melanocyte and melanoma cell biology | Central MC3R/MC4R signaling, energy balance and autonomic models in rodents |
| Regulatory status | Its drug name, afamelanotide, is the active ingredient of an FDA-approved implant for one indication; research material is separate | Not approved by the FDA or any other regulator |
| Full overview | MT-1 research | MT-2 research |
From one hormone to two research tools
Natural alpha-MSH is a linear 13-residue peptide with two weaknesses as a research tool: its methionine at position 4 oxidizes easily, and proteases break it down within minutes. In 1980, Sawyer and colleagues replaced that methionine with norleucine and the L-phenylalanine at position 7 with its D-isomer. The result, later called melanotan 1, was far more potent and longer-acting than the natural hormone (Sawyer et al., 1980).
The same group then asked whether the essential part of the hormone could be made smaller and more rigid. Using molecular dynamics modeling, Al-Obeidi and colleagues designed cyclic analogs in which a lactam bond closes a ring around the His-D-Phe-Arg-Trp core. The best of these became MT-2 (Al-Obeidi et al., 1989). Both molecules keep the D-Phe change, which proved important across the whole melanocortin field.
MT-1: the linear analog
MT-1 keeps the full length of alpha-MSH. It binds the MSH-responsive melanocortin receptors with especially high potency at MC1R, a Gs-coupled receptor that raises cAMP and, in melanocytes, drives enzymes of the eumelanin pathway such as tyrosinase. Cultured melanocytes and melanoma cell lines are its standard research systems (Hadley and Dorr, 2006). As afamelanotide, the compound was developed into a long-acting implant for a rare photosensitivity disorder (Wensink et al., 2021).
Read the full MT-1 research overview or view MT-1.
MT-2: the cyclic analog
MT-2 is about half the length of alpha-MSH, resists enzymatic breakdown, and holds its core residues in a ring that suits several receptor subtypes. It activates MC1R, MC3R, MC4R and MC5R, so it is a broad agonist rather than a selective probe. Researchers use it to switch on melanocortin signaling and then use selective antagonists or knockout animals to find which receptor is responsible. Its main research areas are central MC3R/MC4R circuits and autonomic physiology in rodents (King et al., 2007).
Read the full MT-2 research overview or view MT-2.
Where their research overlaps
- MC1R in cell systems: Both are used in binding and cAMP assays in melanocyte and melanoma cell lines, alongside native alpha-MSH (Sawyer et al., 1980; Hadley and Dorr, 2006).
- Structure-activity research: MT-1 is a standard comparator for newer melanocortin ligands, and MT-2 is a test scaffold for synthesis and cyclization methods (Ryakhovsky et al., 2008).
- Unlicensed products: Dermatology authors have raised concerns about melanotan products sold outside regulated channels, which applies to both names (Langan et al., 2010).
How researchers choose between them
- Studying MC1R signaling in pigment cells: MT-1 is the more MC1R-focused tool.
- Studying central melanocortin circuits (MC3R/MC4R): MT-2 is the standard broad agonist for those rodent models.
- Comparing linear and cyclic ligands: running both shows how ring constraint changes potency and receptor selectivity.
What the research does not show
Receptor, cell-culture and animal data for both describe signaling in model systems and do not establish effects or safety in humans. The approved afamelanotide product is a specific controlled-release implant for one condition, and that approval does not extend to lyophilized research material or to any other use. MT-2 has no approval anywhere. Because MT-2 activates several receptors at once, attributing a response to one receptor requires antagonists, knockouts or more selective compounds. Results for one peptide cannot be assumed for the other, and none of these findings describes the research material sold here.
Verify what you’re working with
The two share their core residues but differ in length and in whether they are cyclized, so identity testing is what tells them apart. Every Rogue batch is tested by an independent, ISO 17025 accredited U.S. lab, and the QR code on each vial opens that batch’s report on the lab’s own website. See how to read a peptide COA or browse the COA Library.
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
- 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
- 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.