Direct Answer
Nonapeptide-1 (trade name Melanostatine-5; INCI Nonapeptide-1) is a synthetic nonapeptide (Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2) identified as a potent antagonist of the α-melanocyte-stimulating-hormone (α-MSH) receptor, the melanocortin-1 receptor (MC1R). By blocking α-MSH signaling it is proposed to reduce melanin synthesis for skin brightening; the receptor pharmacology is well-characterized in vitro, while independent human cosmetic-efficacy data are limited.
Summary Table
Evidence Level
Low
Key Information
Classification
Key Takeaways
- Synthetic brightening nonapeptide (INCI Nonapeptide-1; trade name Melanostatine-5)
- Sequence Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2; CAS 158563-45-2; PubChem CID 10418849 (C61H87N15O9S, MW 1206.50)
- Most potent α-MSH receptor (MC1R) antagonist in the discovery screen — IC50 11 ± 7 nM (Jayawickreme et al., 1994)
- Antagonizing α-MSH/MC1R signaling is proposed to reduce melanin synthesis (brightening)
- Mechanism is well-characterized in vitro; independent human cosmetic-efficacy evidence is limited (low)
- Distinct from Melitane (Acetyl Hexapeptide-1), a different α-MSH-related cosmetic peptide
Scientific Overview
What is Nonapeptide-1 (Melanostatine-5)?
Nonapeptide-1 (INCI Nonapeptide-1; trade name Melanostatine-5) is a synthetic 9-amino-acid peptide, sequence Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2 (CAS 158563-45-2; molecular formula C61H87N15O9S; molecular weight 1206.50 g/mol; PubChem CID 10418849). It was identified in a large peptide-library screen for antagonists of the α-melanocyte-stimulating-hormone (α-MSH) receptor. It is distinct from Melitane (Acetyl Hexapeptide-1), a different cosmetic peptide sometimes discussed alongside it.
In Plain English
Nonapeptide-1, sold as Melanostatine-5, is a lab-made peptide studied as a skin-brightening ingredient. In laboratory receptor tests it was the most potent blocker of MC1R — the receptor the hormone α-MSH uses to tell skin cells to make pigment. Blocking that signal is expected to reduce pigment, which is why it is marketed for brightening. The receptor science is solid in the lab, but there is little independent human evidence that the topical cosmetic actually lightens skin.
Scientific Details
Nonapeptide-1 is a topically marketed cosmetic peptide studied as an α-MSH receptor (MC1R) antagonist for skin brightening. In the discovery study (Jayawickreme et al., J Biol Chem 1994, PMID 7961978), the peptide Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2 was the most potent antagonist in a 31,360-member peptide-library screen, with a reported IC50 of 11 ± 7 nM for blocking α-MSH receptor function; structure–function analysis identified D-Trp5 and Phe6 as crucial, potentiated by D-Phe3. Because α-MSH/MC1R signaling drives melanogenesis, antagonism is proposed to lower melanin synthesis. A review of melanin-modulating peptides (Boo, Biomedicines 2020, PMID 32882959) supports the general plausibility of peptide-mediated melanin downregulation. Independent, controlled human trials of Nonapeptide-1 cosmetic efficacy are not cited; topical efficacy claims rest largely on manufacturer/preclinical materials, so the clinical evidence is limited.
How It Works
Published receptor-pharmacology work (Jayawickreme et al., 1994, PMID 7961978) reports that Nonapeptide-1 acts as an antagonist of the α-MSH receptor (the melanocortin-1 receptor, MC1R), through which α-MSH stimulates pigment (melanin) production in melanocytes. It was the most potent antagonist identified in that screen (IC50 11 ± 7 nM); D-Trp5 and Phe6 were crucial to the antagonism, potentiated by D-Phe3. By blocking α-MSH signaling it is proposed to lower melanogenesis and lighten hyperpigmentation — the rationale for its cosmetic use as "Melanostatine-5." A review of melanin-modulating peptides (Boo, 2020) supports the general plausibility of peptide-mediated melanin downregulation. IMPORTANT: the potent receptor antagonism is an in-vitro finding; topical cosmetic efficacy in humans is limited and rests largely on manufacturer/preclinical materials rather than the independent studies cited here.
Mechanism of Action
α-MSH receptor (MC1R) antagonism
cell
Nonapeptide-1 (Melanostatine-5) was identified as the most potent α-MSH receptor antagonist in a 31,360-member peptide-library screen (Jayawickreme et al., 1994, PMID 7961978), with a reported IC50 of 11 ± 7 nM for blocking α-MSH receptor function; D-Trp5 and Phe6 were crucial to the antagonism, potentiated by D-Phe3. Because α-MSH signaling through the melanocortin-1 receptor (MC1R) drives melanogenesis, antagonizing this receptor is proposed to reduce melanin synthesis (skin brightening). The receptor pharmacology is well-characterized in vitro; downstream cosmetic effects in human skin are not established in the independent literature cited here.
Evidence Level
Human Evidence
No independent, controlled human trial of Nonapeptide-1 is cited. Topical cosmetic (skin-brightening) efficacy rests largely on manufacturer/supplier materials and is not established in the independent literature here.
Animal Evidence
No animal studies are cited for this entry.
Cell Evidence
A receptor-pharmacology study (Jayawickreme et al., 1994, PMID 7961978) identified the peptide as the most potent α-MSH receptor antagonist in a large library screen, with a reported IC50 of 11 ± 7 nM; D-Trp5 and Phe6 were crucial to antagonism.
Limitations
The strong data are in-vitro receptor pharmacology; the cosmetic outcome (reduced pigmentation/brightening) is a proposed downstream effect, supported at the class level by a review (Boo, 2020) but not by an independent human trial of this peptide. Interpret cautiously.
Why This Grade
Rated low: the α-MSH receptor antagonism is real and well-characterized in vitro — a peer-reviewed discovery paper reports IC50 11 ± 7 nM — but there is no independent, controlled human trial of Nonapeptide-1 in the cited literature; topical cosmetic (brightening) efficacy rests on manufacturer/preclinical materials. The mechanism is strong; human cosmetic efficacy for this peptide is limited.
Frequently Asked Questions
What is Nonapeptide-1?
Nonapeptide-1 (trade name Melanostatine-5, INCI Nonapeptide-1) is a synthetic 9-amino-acid peptide (Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2) used in topical skin-brightening products. It was identified as a potent antagonist of the α-melanocyte-stimulating-hormone (α-MSH) receptor, the melanocortin-1 receptor (MC1R).
How is Nonapeptide-1 described to work?
It acts as an antagonist of the α-MSH receptor (MC1R) — the receptor α-MSH uses to stimulate melanin production in skin cells. In the discovery study it was the most potent antagonist found, with a reported IC50 of 11 ± 7 nM. By blocking α-MSH signaling, it is proposed to reduce melanin synthesis and brighten skin. This is primarily an in-vitro receptor finding.
Is there strong human evidence that Nonapeptide-1 brightens skin?
The receptor pharmacology (α-MSH/MC1R antagonism) is well-characterized in the laboratory, but independent controlled human trials of Nonapeptide-1 as a topical cosmetic are limited — brightening-efficacy claims rest largely on manufacturer/preclinical materials. A review of melanin-modulating peptides supports the general mechanism, but the human cosmetic evidence for this specific peptide is limited.
Is Melanostatine-5 the same as Melitane?
No. Melanostatine-5 is a trade name for Nonapeptide-1 (Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2), an α-MSH receptor antagonist. Melitane is a trade name for Acetyl Hexapeptide-1 — a different peptide. They are distinct ingredients and should not be conflated.
References
- Discovery and structure-function analysis of alpha-melanocyte-stimulating hormone antagonists. Journal of Biological Chemistry. (Independent academic research (Yale University School of Medicine, Boyer Center for Molecular Medicine); no formal conflict-of-interest statement in the 1994-era record.)Supports the α-MSH receptor (MC1R) antagonist mechanism and the exact sequence — the discovery / structure–function paper reporting IC50 11 ± 7 nM for the Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2 antagonist.Cell / In VitroPMID: 7961978 →
- Up- or Downregulation of Melanin Synthesis Using Amino Acids, Peptides, and Their Analogs. Biomedicines. (Independent — single-author academic review (Kyungpook National University); the author declares no conflict of interest.)Supports the general, independent-review framing that peptides — including α-MSH-derived sequences — can down-regulate melanin synthesis; it is a review and does not itself test Nonapeptide-1 cosmetic efficacy.Reviewdoi:10.3390/biomedicines8090322 →
Alternative Names
- Melanostatine-5
- Melanostatine
- α-MSH receptor antagonist nonapeptide
Claim Boundaries
ION BLUE is an educational research aggregator. This content summarizes published scientific literature and, where noted, manufacturer/supplier materials. It is not medically reviewed, is not medical advice, and is not a recommendation to use any substance. Consult a licensed healthcare provider. This entry summarizes in-vitro receptor pharmacology and a review; it does not assert established human cosmetic efficacy for Nonapeptide-1 and is not a recommendation to use the ingredient.
This page summarizes published research and is for informational purposes only; it is not medical advice.