Description
Melanotan 2 (MT-2) Research Peptide (10 mg)
Melanotan 2 (MT-2) is a synthetic cyclic heptapeptide analogue of endogenous α-melanocyte-stimulating hormone (α-MSH), developed at the University of Arizona as a structurally minimized, conformationally constrained derivative designed to improve metabolic stability and receptor selectivity relative to the native hormone and its linear analogue Melanotan 1.
MT-2 has been extensively characterized in peer-reviewed research examining melanocortin receptor pharmacology across multiple receptor subtypes, with particular focus on MC1R-mediated pigmentation biology, MC4R-associated neurological signaling, and metabolic regulation pathways.
Structural Characteristics
MT-2 is a cyclic lactam heptapeptide with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂. The cyclization is formed via a lactam bridge between the side chains of Asp⁴ and Lys⁹, constraining the peptide backbone into a stable, bioactive conformation. This cyclization is a key structural distinction from the linear MT-1.
Two additional modifications enhance its pharmacological profile: norleucine (Nle) substitution at position 4 removes the oxidation-prone methionine of native α-MSH, and D-phenylalanine (D-Phe) at position 7 replaces the natural L-Phe residue. This D-amino acid substitution introduces conformational rigidity within the pharmacophore core (His-D-Phe-Arg-Trp) and significantly increases binding affinity across melanocortin receptor subtypes compared to both α-MSH and MT-1.
Characterized Signaling Pathways
Published research has identified multiple receptor-mediated signaling interactions:
MC1R / Melanogenesis (cAMP–PKA–MITF Axis)
MT-2 binds MC1R with high affinity, activating Gs-coupled adenylyl cyclase and elevating intracellular cAMP. PKA activation phosphorylates MITF, driving transcriptional upregulation of tyrosinase, TRP-1, and TRP-2—key enzymes in the eumelanin synthesis pathway. Binding affinity studies demonstrate MT-2 exhibits significantly greater MC1R potency than native α-MSH (Hadley & Dorr, Peptides, 2006).
MC4R / Hypothalamic Energy and Neurological Signaling
MT-2 is a non-selective melanocortin agonist with notable activity at MC4R, which is expressed in hypothalamic nuclei involved in energy homeostasis and autonomic regulation. Research in rodent models has characterized MC4R-mediated effects on food intake suppression, energy expenditure, and autonomic outflow, establishing MT-2 as a widely used pharmacological tool for probing central melanocortin circuitry (Huszar et al., Cell, 1997; Fan et al., Nature, 1997).
MC3R / Peripheral Metabolic Modulation
MT-2 also engages MC3R, expressed in peripheral tissues including adipose, gut, and immune cells. MC3R activation has been associated with regulation of adipogenesis, inflammatory mediator release, and natriuretic signaling in animal model research (Butler et al., Endocrinology, 2000).
Photoprotective and Antioxidant Signaling
Consistent with MC1R engagement, MT-2 has been shown in in-vitro models to reduce UV-induced cyclobutane pyrimidine dimer (CPD) formation and attenuate reactive oxygen species (ROS) accumulation in melanocytes, paralleling the photoprotective signaling profile documented for MT-1 (Abdel-Malek et al., Cancer Research, 2005).
Research Applications
MT-2 has been utilized as a molecular probe in controlled experimental systems examining:
- Melanocortin receptor pharmacology and subtype selectivity (MC1R–MC5R)
- Melanogenesis and pigmentation signaling cascades
- Hypothalamic energy homeostasis and appetite regulation models
- Central melanocortin circuit characterization
- Cutaneous photoprotection and UV-induced DNA damage models
- Peripheral metabolic and adipogenic signaling
- Autonomic nervous system modulation research
