Melanotan-2
10 MGMelanotan-2 (MT2 / MT-II / MTII) — cyclic α-MSH superagonist heptapeptide
Studied therapeutic interests:
Melanotan-2 — also referenced in the literature as MT2, MT-II, MTII, MT-2 or Melanotan II — is a synthetic cyclic heptapeptide (Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂, 1024.18 g/mol) designed as a superagonist analog of the α-MSH melanotropic hormone. Developed at the University of Arizona in the 1990s by the Hadley and Hruby group, MT-II activates melanocortin receptors MC1R, MC3R, MC4R and MC5R with greater metabolic stability than native α-MSH, making it a reference pharmacological tool for the study of melanocortin pathways in in vitro models.
The cyclic structure obtained by a lactam bridge between aspartic acid (position 2) and lysine (position 7) rigidifies the bioactive conformation of the His-Phe-Arg-Trp pharmacophore, common to the melanotropic hormones α-MSH, β-MSH and γ-MSH. The substitution of native methionine by norleucine (Nle) at position 4 and the introduction of D-phenylalanine at position 7 confer remarkable resistance to degradation by serum peptidases.
Preclinical studies published in peer-reviewed journals have demonstrated significant effects on B16-F10 (mouse) and MNT-1 (human) melanocyte lines, where MT-II stimulation at nanomolar concentrations induces a dose-dependent increase in tyrosinase activity and eumelanin production. In HEK-293 recombinant cell models, the EC50 for the MC4R receptor is approximately 0.1 nM, reflecting subnanomolar affinity.
At OSMOSE Research, Melanotan-2 is supplied as a lyophilized powder with HPLC purity ≥ 99.2%, accompanied by a complete certificate of analysis. Manufactured in Europe under GMP standards, this research peptide is delivered to France, Belgium, Switzerland, Luxembourg and worldwide internationally with insulated packaging that preserves molecular stability.
- Preclinical research on melanogenesis and MC1R (B16-F10 models)
- Studies on central food intake regulation via MC4R
- Comparative pharmacology of melanocortin analogs
- In vitro models of cAMP activation and tyrosinase
- Preclinical research on copulatory behavior and MC3R
- Comparative studies with SHU-9119, AgRP and afamelanotide
- Studies on melanocortin receptor desensitization
- Pharmacological characterization of MC1R, MC3R, MC4R, MC5R
Melanotan-2 (MT2, MT-II, MTII) is the most studied melanocortin analog in preclinical research. The foundational work of Hadley, Hruby and Al-Obeidi (1989-present) established its non-selective superagonist profile on MC1R to MC5R, with subnanomolar affinity for MC4R (EC50 ~0.1 nM). Research topics include: melanogenesis via MC1R (B16-F10, MNT-1 lines), central regulation of food intake and energy expenditure via hypothalamic MC4R, exocrine secretion via MC5R, and characterization of the contribution of MC3R to copulatory behavior. Comparative studies with afamelanotide (NDP-α-MSH), SHU-9119 and the endogenous ligand Agouti-Related Protein (AgRP) enrich the dissection of pathway specificity. In vivo, intracerebroventricular (ICV) administration in ob/ob murine models has established the conceptual framework of central leptin-melanocortin pathways (Fan et al., Nature 1997).
- HPLC purity ≥ 99.2% verified by RP-HPLC
- Molecular mass certified by ESI-MS (1024.18 g/mol)
- Endotoxin test < 0.5 EU/mg by LAL method
- Sterility validation
- Cyclization verification (lactam bridge Asp²-Lys⁷)
Frequently asked questions
Yes. MT2, MT-II, MTII, MT-2 and Melanotan II are all abbreviations for the same cyclic heptapeptide Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂ (1024.18 g/mol). These spellings vary by journal and laboratory — they designate the same α-MSH superagonist molecule.
Afamelanotide (NDP-α-MSH) is a 13-residue linear analog with strong MC1R selectivity (Ki ≈ 0.23 nM). MT-II is a 7-residue cyclic analog acting as a non-selective agonist on MC1R through MC5R with subnanomolar affinity for MC4R. MT-II is a privileged tool for central studies, while afamelanotide is preferred for melanogenesis studies.
Cyclization by a lactam bridge between Asp² and Lys⁷ rigidifies the bioactive conformation of the His-Phe-Arg-Trp pharmacophore. This structural preorganization increases affinity for melanocortin receptors and confers greater resistance to exopeptidase enzymatic degradation.
Reference models are the B16-F10 melanocyte line (mouse) and MNT-1 (human) for melanogenesis, HEK-293 transfected with hMC4R for cAMP dosing, and GT1-7 hypothalamic neurons for studies on central feeding regulation.
For MC4R cAMP accumulation dosing, 0.1 to 1 nM is sufficient (EC50 ~0.1 nM). For melanogenesis in B16-F10, 1 to 100 nM over 24-72h. For comparative binding studies, 0.01 to 10 nM. A dose-response curve is recommended for each model.
Melanotan-2 reconstitutes in sterile bacteriostatic water or PBS pH 7.4 (solubility > 1 mg/mL). Typical stock concentration: 10 mg/mL. Avoid vigorous agitation that could denature the cyclic structure. Once reconstituted, stability is 28 days at 4 °C.
For quantitative pharmacology studies (EC50, Ki), purity ≥ 99.2% HPLC is imperative. SPPS synthesis impurities include incorrectly sequenced peptides, non-cyclized linear forms and tryptophan oxidation products — all of which can alter receptor binding measurements.
No. Melanotan-2 is an experimental peptide intended exclusively for in vitro research. It has no MA (ANSM, EMA, FDA). Only afamelanotide (Scenesse®, CUV1647) holds a marketing authorization limited to erythropoietic protoporphyria (PPE) in Europe.
Yes, intracerebroventricular (ICV) administration of MT-II in rodents is a classical model for studying central regulation of food intake and energy expenditure via hypothalamic MC4R. Studies have established the conceptual framework of central leptin-melanocortin pathways.
MT-II has subnanomolar affinity for MC4R: EC50 ~0.1 nM in HEK-293 recombinantly expressing hMC4R. This extreme potency makes it the pharmacological reference for comparing new melanocortin ligands.
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