Melanotan 1, also known as afamelanotide or NDP-alpha-MSH, is a linear 13-residue analogue of alpha-melanocyte-stimulating hormone carrying norleucine at position 4 and D-phenylalanine at position 7. It is an agonist at melanocortin receptors and is the standard reference ligand for MC1R work in melanocyte culture and receptor pharmacology. Melanotan 1 is supplied by NuVion Health as a laboratory chemical for in vitro research use only.
Key facts
| Type / class | Synthetic peptide, linear alpha-MSH analogue |
| Amino acid count | 13 |
| Molecular formula | C78H111N21O19 |
| Molecular weight | 1646.8 g/mol |
| CAS number | 75921-69-6 |
| Synonyms | Afamelanotide, NDP-MSH, NDP-alpha-MSH, [Nle4, D-Phe7]-alpha-MSH |
| Supplied form | Lyophilised powder in a sealed vial |
Melanotan 1
$59 AUD
View productResearch use only. Not for human or veterinary use.
Structure and chemistry
The parent molecule, alpha-MSH, is the first 13 residues of adrenocorticotropic hormone processed from proopiomelanocortin, acetylated at the N terminus and amidated at the C terminus. Melanotan 1 keeps that framework and reads Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. Two positions are changed from the natural sequence, and both changes were made to address problems with the native peptide.
Methionine at position 4 is replaced by norleucine, an isosteric residue with a straight butyl side chain and no sulfur, which removes the oxidation site that makes alpha-MSH awkward to handle and store. Phenylalanine at position 7 is replaced by its D enantiomer. That inversion sits in the middle of the His6-Phe7-Arg8-Trp9 message sequence, the minimal core recognised by every melanocortin receptor, and it stabilises a beta-turn across those four residues while making the backbone a poor substrate for endopeptidases. The result is a peptide with markedly higher receptor affinity than alpha-MSH and much better chemical stability. The molecule is linear, which is the main structural difference from Melanotan 2, where the same message sequence is constrained inside a lactam ring between Asp5 and Lys10. The N-acetyl group and C-terminal amide block exopeptidase attack at both ends, and the tryptophan residue gives a useful absorbance at 280 nm for concentration measurement.
Mechanism of action
Melanocortin receptors MC1R to MC5R are class A G protein-coupled receptors that all couple to Gs. MC1R is the receptor expressed on epidermal melanocytes and is the usual context in which this analogue is used, although the peptide binds MC3R, MC4R and MC5R with high affinity as well, which is why concentration-response comparisons across the family are normally run with subtype-selective controls. MC2R is the exception in the family: it responds to ACTH and not to alpha-MSH analogues, because it requires additional N-terminal ACTH residues and the accessory protein MRAP.
Binding at MC1R activates adenylyl cyclase through Gs and raises cyclic AMP. Protein kinase A phosphorylates CREB, and CREB-dependent transcription raises expression of MITF, the basic helix-loop-helix transcription factor that acts as the master regulator of the melanocyte programme. MITF in turn drives transcription of the melanogenic enzymes tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1) and dopachrome tautomerase (DCT). Tyrosinase hydroxylates L-tyrosine to L-DOPA and oxidises it to dopaquinone inside melanosomes, and the downstream chemistry then partitions between eumelanin and pheomelanin depending on cysteine availability and on the level of MC1R signalling. The endogenous antagonist agouti signalling protein competes at the same site and shifts that partition in the opposite direction.
Two further features make the receptor a common subject of cell-level work. Common MC1R coding variants, including R151C, R160W and D294H, are loss-of-function alleles with reduced coupling to Gs, and they are routinely characterised by expressing each variant in a heterologous line and comparing cAMP output against the wild-type receptor with this peptide as the agonist. Sustained occupancy also produces GRK phosphorylation, beta-arrestin recruitment and receptor internalisation, so the arrestin arm can be measured separately from the cyclase arm in the same cells.
Research applications
- Radioligand binding across MC1R to MC5R, where iodinated NDP-alpha-MSH is the long-standing tracer for saturation and competition experiments.
- cAMP accumulation assays in B16 mouse melanoma cells and in HEK293 lines expressing individual melanocortin receptor subtypes.
- Melanin content assays in cultured melanocytes, quantified by absorbance of alkali-solubilised pigment, alongside tyrosinase activity assays following L-DOPA oxidation.
- Expression work on MITF, TYR, TYRP1 and DCT by qPCR and immunoblot, and melanosome maturation and dendrite transfer studies in melanocyte and keratinocyte co-culture.
- Functional characterisation of MC1R coding variants and of receptor internalisation by BRET or imaging formats.
- RP-HPLC and LC-MS method development, where the acetylated, amidated 13-mer serves as a well-behaved reference analyte.
In the NuVion catalogue it is listed under Reproductive Signalling with the other melanocortin analogues.
Handling in the laboratory
Reconstitute the lyophilised solid with bacteriostatic water, adding solvent down the wall of the vial and swirling gently until dissolved. The reconstitution calculator gives the concentration obtained for a chosen solvent volume. Keep sealed vials of lyophilised material dry, away from light and refrigerated as described in the product documentation, and keep reconstituted solution refrigerated and use it within the period that documentation states. The tryptophan residue is light-sensitive, so amber tubes or foil are sensible for stock solutions, and aliquoting limits repeated freeze-thaw. Working dilutions at nanomolar concentrations call for low-binding plasticware or carrier protein in the buffer. Material is characterised by RP-HPLC for purity and by mass spectrometry for identity.
Testing and supply from NuVion
NuVion Health has material independently tested by Janoshik Analytical, with purity measured by RP-HPLC and identity by mass spectrometry. Most batches are tested and the Certificate of Analysis for a tested batch is published on the product page, with the wider collection in the certificate of analysis library. Manufacture is GMP-audited, vials are supplied lyophilised and sealed, and orders are dispatched from within Australia.
Related compounds
The obvious comparator is Melanotan 2, the cyclic lactam analogue of the same message sequence, and PT-141, a cyclic melanocortin peptide characterised mainly at MC4R and MC3R.
Frequently asked questions
What is Melanotan 1 used for in research?
It is used as a melanocortin receptor agonist in binding and cAMP assays, and as the reference agonist in melanocyte culture work on tyrosinase activity, melanin content and MITF-driven gene expression. Its iodinated form is a standard tracer in receptor binding panels.
How does Melanotan 1 differ from Melanotan 2?
Melanotan 1 is a linear 13-residue peptide with the full alpha-MSH backbone. Melanotan 2 is a shorter cyclic peptide in which a lactam bridge between Asp5 and Lys10 constrains the message sequence, which changes its profile across the receptor subtypes.
Is Melanotan 1 a therapeutic good in Australia?
No. The material supplied here is a laboratory chemical. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration. It is sold for in vitro laboratory research and for no other purpose.
How should Melanotan 1 be stored?
Keep the sealed vial of lyophilised peptide dry, away from light and refrigerated as set out in the product documentation. Once reconstituted, keep the solution refrigerated, shielded from light, and use it within the period stated in that documentation.
Research use only. This product is a laboratory chemical supplied for in vitro research. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. It is not for human or veterinary use, and nothing on this page is a representation about therapeutic use.
