Melanotan 2
Cyclic heptapeptide synthetic analogue of α-melanocyte-stimulating hormone (α-MSH). Agonist at MC1R (melanocytes — melanogenesis) and MC4R (hypothalamus — appetite and autonomic pathways). Cyclic structure confers metabolic stability compared to linear α-MSH. Studied in pigmentation, receptor pharmacology, and hypothalamic signalling research.
Mechanism of Action
Melanotan II (MT-II) is a cyclic heptapeptide designed as a metabolically stable analogue of the endogenous peptide α-melanocyte-stimulating hormone (α-MSH). The cyclic structure is formed through a lactam bridge between the side chains of Asp5 and Lys10, which constrains the bioactive conformation and substantially reduces susceptibility to enzymatic degradation compared to the linear parent peptide. This structural modification is studied as the basis for MT-II’s enhanced potency and duration of receptor activation relative to native α-MSH.
MT-II acts as an agonist at multiple melanocortin receptor subtypes, with highest affinity at MC1R and MC4R. MC1R is expressed on melanocytes, the pigment-producing cells of skin and hair follicles. MC1R activation stimulates adenylyl cyclase, elevating intracellular cAMP, which activates protein kinase A (PKA). PKA phosphorylates MITF (microphthalmia-associated transcription factor), promoting transcription of melanogenic enzymes including tyrosinase, TRP-1, and TRP-2. The net effect is increased production of eumelanin (brown-black pigment) rather than phaeomelanin (red-yellow pigment). This pathway constitutes the primary molecular cascade studied in pigmentation research using MT-II.
MC4R is expressed predominantly in the hypothalamus, particularly in the paraventricular nucleus (PVN) and lateral hypothalamic area. MC4R signalling via the hypothalamic melanocortin system is studied for roles in energy homeostasis and feeding behaviour — the MC4R pathway antagonises the orexigenic effects of AgRP and NPY. MC4R expression in the paraventricular nucleus and medial amygdala also represents the neuroanatomical substrate for studying MT-II effects on autonomic nervous system signalling in preclinical research models.
Key Research Findings
- MC1R agonism and melanogenesis pathway activation by Melanotan II has been documented in multiple pigmentation research models, including melanocyte cell cultures and in vivo rodent pigmentation studies establishing the cAMP/PKA/MITF/tyrosinase signalling cascade. Hadley and Hruby research group, University of Arizona, α-MSH analogue and melanocortin pigmentation literature, 1980s–1990s.
- MC4R-mediated effects in rodent models of energy homeostasis have been studied extensively, with published work documenting suppression of feeding behaviour and modulation of energy expenditure through hypothalamic MC4R circuits. Cone research group, Vanderbilt University, MC4R energy balance literature.
- Penile erection response in rodent models attributable to MC4R activation in the paraventricular nucleus has been documented in pharmacological research, establishing the CNS autonomic pathway research relevance of MT-II as a tool compound for melanocortin receptor biology. Argiolas and Melis research group, paraventricular nucleus melanocortin literature.
- Skin pigmentation studies in human subjects were conducted during initial peptide development research at the University of Arizona; subsequent focus shifted toward receptor pharmacology and structure-activity relationship characterisation. Hadley and Hruby, University of Arizona α-MSH development literature, 1980s–1990s.
- Structure-activity relationship research comparing cyclic versus linear α-MSH analogues has characterised the contributions of the cyclic lactam structure to receptor affinity, metabolic stability, and selectivity across the melanocortin receptor family. Hruby et al., melanocortin SAR literature, Journal of Medicinal Chemistry, 1990s.
Citations last reviewed: 1 October 2026
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Researcher FAQ
What is Melanotan 2?
Melanotan II (MT-II) is a synthetic cyclic heptapeptide analogue of α-melanocyte-stimulating hormone (α-MSH). It acts as an agonist at melanocortin receptors, particularly MC1R (expressed in melanocytes, responsible for melanogenesis) and MC4R (expressed in hypothalamus, studied for appetite and autonomic pathway modulation). The cyclic structure confers metabolic stability compared to linear α-MSH.
What are melanocortin receptors in a research context?
Melanocortin receptors (MC1R–MC5R) are a family of Gs-coupled GPCRs activated by melanocortin peptides including ACTH and α-MSH. MC1R in melanocytes governs eumelanin production through the cAMP/PKA/MITF/tyrosinase pathway. MC4R in hypothalamic circuits is studied for energy homeostasis and feeding behaviour. MC2R is the ACTH receptor in adrenal cortex. MC3R and MC5R have distinct tissue distributions with research roles in energy balance and exocrine gland function respectively.
How is Melanotan 2 reconstituted and stored?
Supplied as lyophilised powder, stored at −20 °C. Reconstitution in sterile bacteriostatic water is standard for research use, gently swirling until dissolved. Reconstituted solution stored at 2–8 °C and used within 28 days per experimental protocol. Avoid repeated freeze-thaw cycles of reconstituted material.
What research category does Melanotan 2 belong to?
Melanotan 2 is classified under longevity and pigmentation research. Primary investigational areas include melanocortin receptor pharmacology, melanogenesis signalling, MC4R-mediated hypothalamic pathway research, and structure-activity relationship studies of α-MSH analogues.
Does BasedPeps provide purity documentation?
Yes. Every BasedPeps lot includes a third-party Certificate of Analysis documenting HPLC purity (≥99%) and mass spectrometric identity confirmation. Certificates of Analysis are available per batch on request.
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Research-grade cyclic α-MSH analogue. Third-party HPLC and mass spectrometry verification per lot. Certificate of Analysis available on request. Dispatched from Riga, Latvia within 24 hours.
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