Melanotan I

What is Melanotan I?

Melanotan I is a synthetic linear tridecapeptide analogue of alpha-melanocyte-stimulating hormone, sequence Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂ (C₇₈H₁₁₁N₂₁O₁₉, 1646.9 g/mol, CAS 75921-69-6), catalogued in the literature as afamelanotide, as NDP-alpha-MSH, and in analogue notation as [Nle⁴, D-Phe⁷]-alpha-MSH. It was first reported by Sawyer, Hruby, Hadley and colleagues in the Proceedings of the National Academy of Sciences in 1980. Only two of the thirteen residues differ from the native human hormone: norleucine replaces the oxidation-prone methionine at position 4, and the phenylalanine at position 7 is inverted to its D-enantiomer inside the conserved His-Phe-Arg-Trp message tetrapeptide. There is no lactam bridge, so unlike Melanotan II the mt1 peptide is fully linear. Afamelanotide is authorised as a medicine in certain jurisdictions outside the UK. The material supplied here is not a medicine, holds no UK marketing authorisation, and is supplied as lyophilised powder strictly for in-vitro laboratory research use only, not for human or veterinary administration.

Melanotan 1 vs Melanotan II vs alpha-MSH

These three bracket the melanocortin agonist landscape and are constantly confused, so it is worth setting the chemistry out plainly. Native human alpha-MSH is the 13-residue parent, Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂, with a methionine at position 4 that is the most oxidation-prone group in the molecule and an all-L backbone that peptidases cleave readily. Melanotan 1 keeps all thirteen residues and changes two of them, Nle⁴ for Met⁴ and D-Phe⁷ for L-Phe⁷, which is why the 1980 characterisation described it as an alpha-melanotropin with unusually prolonged activity. Melanotan II takes a different route, truncating to the alpha-MSH 4-10 fragment and closing a lactam bridge between the Asp5 side-chain carboxyl and the Lys10 side-chain amine to give a 23-membered macrocycle (C₅₀H₆₉N₁₅O₉, 1024.2 g/mol, CAS 121062-08-6). The pharmacological consequence is the part that matters. Curated data place Melanotan 1 as a full agonist at four subtypes with a clear order-of-magnitude preference for MC1R: pIC₅₀ 10.0 at MC1R, pKi 8.9 at MC3R, pKi 8.5 to 8.8 at MC4R, pIC₅₀ 9.0 at MC5R, and no activity at MC2R. Cyclisation in Melanotan II flattens that profile, giving comparable potency at MC1R and MC4R and only modestly less at MC3R and MC5R, which is why Melanotan II is used as the non-selective positive control while Melanotan 1 is used where an MC1R-weighted reference agonist is wanted. Neither is subtype-selective in the strict sense, and all three are distinct chemical entities with distinct CAS numbers.

Melanotan I Research Applications

Melanotan I occupies a specific and unusually load-bearing position in melanocortin receptor pharmacology, because its radioiodinated form is the field's default radioligand. A very large fraction of published binding constants for melanocortin ligands, including those for cyclic analogues, peptidomimetics and candidate subtype-selective compounds, are reported as inhibition of ¹²⁵I-NDP-alpha-MSH binding to membranes from cell lines stably expressing a single human receptor subtype. The unlabelled peptide is used alongside it as a full-agonist reference point in cAMP accumulation assays, since all five melanocortin receptors are class A G-protein-coupled receptors signalling principally through Gs and adenylyl cyclase. Beyond assay plumbing, the molecule is a structure-activity reference in three recurring contexts: as the linear counterpoint against which conformationally constrained analogues are benchmarked, which is how the value of the Asp5 to Lys10 lactam bridge in the Melanotan II family was originally quantified; as a probe of the D-Phe⁷ stereocentre, the single inversion that both stabilises the bioactive turn of the His-Phe-Arg-Trp core and removes a favoured chymotrypsin-like cleavage point; and as a structural biology ligand, with cryo-EM structures of full-length MC4R in complex with heterotrimeric Gs resolving afamelanotide in the orthosteric pocket alongside alpha-MSH and describing a conserved binding mode for peptidic melanocortin agonists. All of this is receptor-level characterisation in transfected cell systems and recombinant complexes, and none of it constitutes evidence of any effect in humans.

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 I 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. Note that the norleucine substitution at position 4 has already removed the methionine thioether present in native alpha-MSH, so tryptophan governs handling. The molecule carries both a tryptophan and a tyrosine 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 I should be kept protected from UV and fluorescent light in both lyophilised and reconstituted form. Tryptophan oxidation is the degradation route most commonly detected by RP-HPLC in stored melanocortin analogues, with tyrosine at position 2 and histidine at position 6 secondary sites 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

• 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone, a highly potent alpha-melanotropin with ultralong biological activity (Proc Natl Acad Sci USA, 1980)
• Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors (Eur J Pharmacol, 1999)
• Structural insights into ligand recognition and activation of the melanocortin-4 receptor (Cell Res, 2021)

Related Research Compounds

• → Melanotan II 10mg
• → PT-141 10mg
• → Bacteriostatic Water 10ml