What Is Melanotan 2?
Melanotan 2 (MT-II) is a synthetic cyclic heptapeptide analogue of alpha-melanocyte stimulating hormone (α-MSH). Developed at the University of Arizona in the 1980s as part of a programme investigating photoprotection strategies, MT-II is a non-selective melanocortin receptor agonist that has since become a significant tool compound in melanogenesis, appetite, and neuroendocrine research.
Molecular Structure and Properties
- Full name: [Nle4, D-Phe7]-alpha-MSH (cyclic)
- Structure: Cyclic heptapeptide — Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂
- Molecular weight: ~1,024 Da
- Parent compound: α-MSH (13-amino acid linear peptide, endogenous POMC derivative)
- Key modifications: Norleucine at position 4, D-Phe at position 7, cyclisation — increase potency and metabolic stability vs. native α-MSH
- Supplied as: lyophilised powder for in vitro research use
Mechanism of Action: Melanocortin Receptor Agonism
Melanotan 2 is a non-selective agonist at the melanocortin receptor family (MC1R–MC5R), which are GPCRs coupled to Gs proteins. Receptor activation increases intracellular cAMP via adenylyl cyclase stimulation, initiating downstream PKA-mediated signalling. The primary research-relevant receptor subtypes are:
MC1R — Melanogenesis:
- MC1R is expressed on melanocytes and governs the switch between eumelanin (brown/black) and phaeomelanin (red/yellow) production
- MT-II binding increases cAMP → PKA activation → MITF (microphthalmia-associated transcription factor) upregulation → tyrosinase, TRP-1, and TRP-2 expression → eumelanin synthesis
- This makes Melanotan 2 the primary tool compound in in vitro melanogenesis models and pigmentation research
MC4R — Appetite and Energy Regulation:
- MC4R is expressed in the hypothalamus and plays a central role in appetite suppression, energy expenditure, and metabolic regulation
- MT-II’s MC4R agonism has been studied in preclinical models of obesity, food intake regulation, and energy homeostasis
- MC4R is also involved in autonomic nervous system regulation and has been studied in the context of sexual function biology
MC3R — Energy Homeostasis and Immune Modulation:
- MC3R is expressed in hypothalamus and peripheral tissues; involved in energy balance and immune cell signalling
MC5R — Exocrine Gland Function:
- MC5R expressed in exocrine glands; studied in the context of sebaceous gland function and lacrimal gland biology
Key Research Areas
Melanogenesis and pigmentation research: MT-II is the standard tool compound for in vitro melanocyte biology. It is used to study pigmentation signalling cascades, MITF regulation, melanin quantification assays, and the genetics of skin colour variation. Its high potency at MC1R and resistance to enzymatic degradation (vs. native α-MSH) make it particularly suitable for long-duration cell culture experiments.
Photoprotection biology: The original University of Arizona research programme that produced MT-II was investigating systemic melanogenesis as a photoprotective strategy. Subsequent research has examined the relationship between MC1R activation, eumelanin density, and UV-induced DNA damage in keratinocyte and melanocyte models.
Appetite and metabolic research: MT-II’s MC4R agonist activity has been studied in rodent models of diet-induced obesity. Pierroz et al. and subsequent researchers demonstrated reduced food intake and body weight in MC4R-expressing preclinical models following MT-II administration, supporting MC4R as a target in metabolic disease research.
Neuroendocrine research: MT-II’s central effects via hypothalamic melanocortin receptors (MC3R, MC4R) have made it a tool compound in studies examining the POMC/AgRP/NPY circuit that regulates energy homeostasis and autonomic function.
Research Status
Melanotan 2 was investigated in early Phase I/II clinical trials at the University of Arizona for photoprotection and erectile dysfunction indications, establishing human pharmacokinetic data. Bremelanotide (PT-141), a related melanocortin agonist derived from MT-II research, received FDA approval in 2019 for hypoactive sexual desire disorder — validating the melanocortin receptor as a clinically relevant target. MT-II itself remains a research compound.
Sourcing Melanotan 2 for Research
R&D Peptides supplies Melanotan 2 10mg as a lyophilised research compound with a batch-specific Certificate of Analysis. Supplied strictly for in vitro research use only.
For quality and testing standards, see our quality and testing page.
All content on this page is for educational and informational purposes only. Melanotan 2 is supplied by R&D Peptides strictly for in vitro research use. It is not intended for human or veterinary administration, and no therapeutic claims are made or implied.
