Melanotan II

What is Melanotan II?

Melanotan II is a synthetic cyclic lactam heptapeptide analogue of alpha-melanocyte-stimulating hormone, sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂ (C₅₀H₆₉N₁₅O₉, 1024.2 g/mol, CAS 121062-08-6). It was designed by Al-Obeidi, Castrucci, Hadley and Hruby and reported in the Journal of Medicinal Chemistry in 1989, using quenched molecular dynamics to select which conformation of the alpha-MSH 4-10 message sequence to constrain. Three changes distinguish it from the native fragment: a lactam bridge between the Asp5 side-chain carboxyl and the Lys10 side-chain amine, inversion to D-phenylalanine at position 7, and norleucine in place of the oxidation-prone methionine at position 4. Melanotan II is not a licensed medicine in the United Kingdom or any other jurisdiction. It is supplied as lyophilised powder strictly for in-vitro laboratory research use only, and is not for human or veterinary administration.

Melanotan II vs Melanotan I vs SHU-9119

These three compounds bracket the melanocortin ligand landscape and are frequently confused. Melanotan I (afamelanotide, NDP-alpha-MSH) is a linear tridecapeptide analogue of the full alpha-MSH sequence and retains comparatively greater MC1R preference. Melanotan II is a cyclic lactam built on the truncated 4-10 fragment; cyclisation broadens agonist activity across MC1R, MC3R, MC4R and MC5R and increases resistance to proteolytic cleavage, giving the non-selective profile that makes it the usual positive-control agonist in receptor assays. SHU-9119 is the same MT-II scaffold with D-2-naphthylalanine substituted at position 7, a single change that converts it from a full agonist into an MC3R and MC4R antagonist while remaining an agonist at MC1R and MC5R. The MT-II scaffold has since generated a large derivative family through substitutions at positions 6, 7 and 9, including N-methylated variants used to obtain MC1R selectivity. Researchers should treat all three as distinct chemical entities with distinct CAS numbers, not interchangeable options.

Melanotan II Research Applications

Melanotan II is used in vitro as a non-selective reference agonist for the human melanocortin receptor family. The five subtypes (MC1R to MC5R) are class A G-protein-coupled receptors that signal principally through Gs and adenylyl cyclase to raise intracellular cAMP, and the conserved His-Phe-Arg-Trp core of alpha-MSH is the message sequence recognised by the binding pocket. Reported EC₅₀ values for MT-II in transfected cell assays fall in the sub-nanomolar to low-nanomolar range at MC1R and MC4R, roughly an order of magnitude weaker at MC3R and MC5R, and it is essentially inactive at MC2R, the adrenocorticotropin receptor. Because it is potent at four subtypes and selective for none, MT-II serves three specific functions in the literature: as the positive-control full agonist against which candidate subtype-selective ligands are benchmarked in binding and cAMP accumulation assays; as the parent scaffold for structure-activity studies probing positions 5 through 10; and as a conformational reference in NMR and molecular dynamics work on the bioactive turn geometry of constrained melanotropins. Its original characterisation used isolated amphibian and reptilian skin bioassays before the cloned human receptors were available, and those historic potency data remain the reason the compound is described as superpotent in the older literature.

Reconstitution Guide

Allow vials to reach room temperature, then sterilise the rubber stopper of both the peptide vial and the bacteriostatic water vial with an alcohol swab. Slowly draw your bacteriostatic water into a sterile insulin syringe, then inject it gently down the inner glass wall of the peptide vial, never directly onto the lyophilised powder. Once added, gently swirl the vial in a slow circular motion until fully dissolved. Never shake or vortex. The solution should be clear and colourless. Label the vial with the reconstitution date and store immediately. Melanotan II is photolabile, principally through oxidation of the tryptophan residue at position 9, so reconstitute away from direct sunlight and fluorescent lighting and transfer aliquots into amber or foil-wrapped vessels. The single tryptophan residue also gives a usable chromophore, so concentration can be verified by UV absorbance at 280 nm where assay design requires it.

See our full peptide reconstitution guide and reconstitution calculator for step-by-step protocol.

Storage Instructions

Lyophilised vials should be stored at -20°C, protected from light and moisture, and remain stable for up to 24 months. Once reconstituted with bacteriostatic water, store the solution at 2-8°C (standard refrigerator) and use within approximately 3 months. For storage beyond that, prepare single-use aliquots at -20°C, where reconstituted peptide remains stable for up to 6 months. Avoid repeated freeze-thaw cycles and always handle under sterile laboratory conditions. Melanotan II should be kept protected from UV and fluorescent light in both lyophilised and reconstituted form. Tryptophan oxidation is the most common degradation route detected by RP-HPLC in stored melanocortin analogues, with histidine a secondary site of concern, and freeze-thaw cycling accelerates both aggregation and oxidative degradation. Prepare single-use aliquots rather than repeatedly accessing one stock vial.

Frequently Asked Questions

Research References

• Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin, design based on molecular dynamics (J Med Chem, 1989)
• Selectivity of cyclic D-Nal7 and D-Phe7 substituted MSH analogues for the melanocortin receptor subtypes (Peptides, 1997)
• Ligands for Melanocortin Receptors, Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin (Biomolecules, 2022)

Related Research Compounds

• → GHK-Cu 100mg
• → Bacteriostatic Water 10ml