Melanotan I: NDP-MSH Alpha-MSH Analog Research Overview

Endogenous α-MSH is a 13-amino acid peptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂) derived from proopiomelanocortin (POMC). It binds melanocortin receptors, particularly MC1R on melanocytes, where it stimulates melanin production.^[1]

Native α-MSH has limited use as a research tool due to its short half-life — the methionine and aromatic residues are degraded rapidly by tissue proteases. Melanotan I was developed by Hadley, Hruby and colleagues in the early 1980s as a stabilized analog with two key substitutions: norleucine (Nle) for methionine at position 4, and D-phenylalanine for L-phenylalanine at position 7.^[2]

Melanotan I is studied as a research reference compound in preclinical melanocortin receptor pharmacology and pigmentation research. It has not been approved by the FDA for any human therapeutic or medical purpose.

Melanotan I structural features:

• Sequence: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂ (13 residues with two non-natural substitutions)

• Substitutions: Nle⁴ (replacing Met⁴), D-Phe⁷ (replacing L-Phe⁷)

• Length: 13 amino acids (linear, like native α-MSH)

• N-terminus: acetylated

• C-terminus: amidated

• Molecular weight: approximately 1,646 Da

Methionine 4 is susceptible to oxidation and to cleavage by tissue proteases. Replacing it with norleucine — which has similar steric properties but lacks the sulfur atom — eliminates these vulnerabilities while preserving receptor binding.^[2]

Position 7 D-phenylalanine (vs the natural L-form) provides resistance to proteolytic cleavage at this peptide bond. The change also modestly alters backbone geometry, which is reported to enhance receptor affinity and prolong activity in preclinical preparations.

Melanotan I is a pan-agonist at the melanocortin receptor family.

MC1R is the receptor on melanocytes responsible for melanin production. Melanotan I binds MC1R with high affinity and activates Gs-coupled cAMP signaling, leading to tyrosinase expression and downstream melanin synthesis. This is the most extensively characterized activity of the compound.^[3]

Melanotan I shows pan-agonist activity at MC3R, MC4R, and MC5R in cell-based receptor binding assays, though with varying potency. This contrasts with later analogs like Melanotan II (cyclic) which were designed for different selectivity profiles.^[4]

Melanotan I research focuses on melanogenesis and melanocortin receptor pharmacology.

Cultured melanocyte cell lines (B16, MNT-1) are common substrates for Melanotan I research. Endpoints include tyrosinase activity, melanin content, MITF expression, and melanocyte morphology.^[5]

Melanotan I is widely used as a reference agonist in studies characterizing new melanocortin receptor pharmacology, including studies of receptor crystal structures, ligand binding kinetics, and downstream signaling.^[4]

Preclinical studies have examined Melanotan I in rodent models of UV exposure, with endpoints measuring pigmentation response and skin damage markers.^[6]

Melanotan I's substitutions provide enhanced stability over native α-MSH. Standard peptide handling applies.

Lyophilized material is stored at minus 20 degrees Celsius. Brief refrigerated storage is acceptable.

Bacteriostatic water is the standard reconstitution solvent.

HPLC for purity, mass spectrometry for identity confirmation matching the modified mass, and endotoxin screening. Each batch of Instant Peptides Melanotan I ships with a full Certificate of Analysis.

Instant Peptides supplies Melanotan I as a synthetic lyophilized reference compound in 10mg vials. Material is supplied to qualified research professionals. Not for human or animal consumption.

View the product page for current pricing and the Certificate of Analysis for the active batch.