Multi-Receptor Melanocortin Agonism
Melanotan II — Cyclic Melanocortin Analog
Melanotan II (MT2) is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH), developed at the University of Arizona in the 1980s as part of a research program aimed at creating potent, stable melanocortin receptor agonists. Unlike its linear predecessor Melanotan I (afamelanotide), MT2 incorporates a lactam bridge between the aspartate and lysine residues, creating a cyclic structure that confers both increased receptor binding potency and a distinct receptor selectivity profile.
MT2 is distinguished from MT1 by its broader melanocortin receptor activity: while MT1 is highly selective for MC1R, MT2 activates MC1R, MC3R, MC4R, and MC5R. This broader receptor engagement profile gives MT2 a more complex pharmacological profile and has made it a valuable research tool for studying the diverse physiological roles of the melanocortin system.
MT2 is a cyclic 7-amino-acid peptide with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2. The cyclic structure is formed by a lactam bond between the side chains of aspartate (position 2) and lysine (position 7). This cyclization is a key structural feature that increases receptor binding affinity and metabolic stability compared to linear analogs.
Additional structural modifications include: norleucine (Nle) substitution at position 1 to prevent oxidative degradation, D-phenylalanine at position 4 to enhance receptor binding, and N-terminal acetylation with C-terminal amidation. The molecular weight is 1,024.18 Daltons.
MT2 exerts its primary effects through agonism at multiple melanocortin receptor subtypes. At MC1R on melanocytes, it stimulates the cAMP/PKA/MITF pathway to increase eumelanin production, similar to MT1. At MC3R and MC4R in the central nervous system — particularly in the hypothalamus — MT2 modulates appetite, energy homeostasis, and sexual function through pathways involving the melanocortin system's interaction with neuropeptide Y (NPY) and agouti-related protein (AgRP) signaling.
The MC4R-mediated effects are of particular research interest: MC4R activation in the hypothalamus reduces food intake and increases energy expenditure, and has been extensively studied in the context of obesity research. MC4R is also expressed in the spinal cord and peripheral nervous system, where its activation has been linked to pro-erectile signaling through nitric oxide pathways.
MT2 (Melanotan II) is a synthetic peptide related to MT1, but with a key structural difference: it's cyclic (ring-shaped) rather than linear. This structural change gives it a broader range of receptor targets, making it a more pharmacologically complex compound with a wider range of studied effects.
While MT1 primarily targets one receptor (MC1R) for melanogenesis, MT2 activates four melanocortin receptors: MC1R (skin pigmentation), MC3R and MC4R (in the brain, affecting appetite and energy), and MC5R. The MC4R activation in the hypothalamus is of particular research interest because MC4R is a well-validated target in obesity and metabolic research — it's one of the most studied receptors in appetite regulation.
MT2's broader receptor profile makes it a valuable research tool for studying the melanocortin system as a whole, rather than just skin biology. The fact that a single structural modification (cyclization) dramatically changes which receptors a peptide activates is exactly the kind of structure-activity relationship that makes MT2 scientifically interesting beyond its surface-level effects.
MT2 has a more complex and less clinically validated profile than MT1. Unlike MT1, it has not received regulatory approval for any indication. Its broader receptor activity means researchers need to account for a wider range of potential effects. It is supplied strictly for qualified laboratory research use only.
Activates MC1R on melanocytes, driving cAMP/PKA/MITF cascade and increasing eumelanin production.
MC4R agonism in the hypothalamus modulates NPY/AgRP signaling to reduce food intake and increase energy expenditure.
Spinal and peripheral MC4R activation stimulates nitric oxide pathways associated with erectile function in preclinical models.
MC3R activation contributes to anti-inflammatory and immune-modulatory effects observed in preclinical studies.
Skin & Anti-Aging Research
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| Peptide Class | Cyclic heptapeptide α-MSH analog |
| Molecular Weight | 1,024.18 Da |
| Receptor Targets | MC1R, MC3R, MC4R, MC5R |
| Key Structural Feature | Lactam bridge cyclization (Asp²–Lys⁷) |
| Available Sizes | 10mg vials |
| Form | Lyophilized powder |
| Purity | ≥99% (third-party tested) |
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Purchase MT2 at Purgo LabsMedical Disclaimer: All content on this site is for educational and research purposes only. Research peptides are not FDA-approved for human use. Always consult a qualified healthcare professional before considering any peptide or supplement protocol. Nothing on this site constitutes medical advice, diagnosis, or treatment.
