Nonapeptide-1

Also known as: Melanostatine 5, Melanostatine-5, Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2

Evidence: Preclinical

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Overview

Synthetic alpha-MSH(5-13) analog (Melanostatine 5) found in a 1994 library screen as a potent alpha-MSH receptor antagonist (IC50 11 nM); human data are limited to one combination-cream pilot.

Nonapeptide-1 (Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2) was the most potent antagonist found when Lerner's group screened a 31,360-member library built on the alpha-MSH(5-13) sequence, with an IC50 of 11 nM (Jayawickreme et al., 1994). It is sold for cosmetics as Melanostatine 5. The one human study is a 46-person randomized pilot of a cream combining it with phenylethyl resorcinol, another depigmenting agent and sunscreen, versus sunscreen alone after triple-combination therapy for melasma; melanin index and severity scores did not differ significantly (Chatterjee et al., 2021). Its effect alone in human skin has not been published.

Benefits

Alpha-MSH receptor antagonism (in vitro), melasma maintenance as part of a multi-ingredient cream (human pilot RCT, not significant vs sunscreen)

Dosing reference

Research dose: Topical only; no published study states an effective concentration of nonapeptide-1 alone. No oral or injectable dose exists.

Sold as a topical brightening ingredient, usually in a dextran solution (Melanostatine 5). The combination-cream pilot does not give the peptide concentration in its abstract.

Mechanism

Proposed competitive antagonism at the alpha-MSH (melanocortin 1) receptor. In the screen that identified it, D-Trp at position 5 and Phe at position 6 were required for antagonism, which D-Phe at position 3 enhanced (Jayawickreme et al., 1994). The screen used a melanophore receptor assay; reduced cAMP, tyrosinase activity or melanin in human melanocytes treated with nonapeptide-1 alone has not been published. A 2024 study used it as a targeting ligand on silica nanoparticles carrying EGCG, so its own effect there cannot be separated (Huang et al., 2024).

Evidence

Preclinical: animal or in vitro data only

Most potent of a 31,360-peptide alpha-MSH(5-13) library: IC50 11 nM as an alpha-MSH receptor antagonist (Jayawickreme et al., 1994)
Used as the targeting ligand on EGCG-loaded silica nanoparticles that reduced melanin in UV-exposed skin cells and mice; the peptide's own share was not tested (Huang et al., 2024)
Randomized double-blind pilot, 46 melasma patients: a cream containing nonapeptide-1 plus other actives and sunscreen did not significantly beat sunscreen alone on melanin index (Chatterjee et al., 2021)
Human-trial status: no trial of nonapeptide-1 alone; the only RCT tests a multi-ingredient cream and missed significance on its main measures

References

Side effects

The 46-person combination-cream pilot reported no added safety problems (Chatterjee et al., 2021); no study of the peptide alone has assessed safety. Commonly reported (anecdotal): mild irritation or redness.

Storage

Storage: Room temperature, away from light
Lyophilized: 2 years at room temp
Reconstituted: N/A (ready to use)

Pharmacology

Half-life: No published pharmacokinetic data in any species
Bioavailability: Not measured; skin penetration of nonapeptide-1 has not been published
Molecular weight: 1206.52 Da
Sequence: Met-Pro-[D-Phe]-Arg-[D-Trp]-Phe-Lys-Pro-Val-NH2