Cosmetic Grade Peptides Nonapeptide-1 Powder
nonapeptide-1
Nonapeptide-1 (Melanostatine-5)
Product Overview
Nonapeptide-1 (INCI name), also known as Melanostatine-5, Melitane, or 九肽-1, is a synthetic biomimetic nonapeptide composed of nine amino acids: methionine, proline, D-phenylalanine, arginine, D-tryptophan, phenylalanine, lysine, proline, and valine amide. It is a highly selective antagonist of the melanocortin-1 receptor (MC1R) that functions as a competitive inhibitor of α-melanocyte stimulating hormone (α-MSH).
Discovered in the early 1990s through structure–function analysis of α-MSH antagonists by researchers at the University of Michigan and pharmaceutical companies, Nonapeptide-1 was originally developed for its antimicrobial activities. Subsequent animal research revealed that Nonapeptide-1 can potently inhibit melanin synthesis, making it of significant interest for treating skin hyperpigmentation conditions.
Nonapeptide-1 is listed in China’s Inventory of Used Cosmetic Ingredients (IECIC) under serial No. 03642, has been reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel, and is also included in the EU CosIng database.
Chemical & Physical Specifications
Parameter | Specification |
|---|---|
INCI Name | Nonapeptide-1 |
CAS No. | 158563-45-2 |
EINECS/ELINCS No. | Not assigned (000-000-0) |
COSING REF No. | 57418 |
Molecular Formula | C₆₁H₈₇N₁₅O₉S |
Molecular Weight | 1206.5 – 1206.52 g/mol |
Exact Mass | 1205.653 g/mol |
IUPAC Chemical Name | (S)-1-(L-methionyl)-N-((R)-1-(((S)-1-(((R)-1-(((S)-1-(((S)-6-amino-1-((S)-2-(((S)-1-amino-3-methyl-1-oxobutan-2-yl)carbamoyl)pyrrolidin-1-yl)-1-oxohexan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)amino)-5-(diaminomethyleneamino)-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)pyrrolidine-2-carboxamide |
Amino Acid Sequence | Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH₂ |
Shortened Sequence | MPFRWFKPV |
Three‑Letter Sequence (Full) | H-Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH₂ |
Full Chemical Name | L-Methionyl-L-prolyl-D-phenylalanyl-L-arginyl-D-tryptophyl-L-phenylalanyl-L-lysyl-L-prolyl-L-valinamide |
Synonyms | Melanostatine-5, Melitane, 九肽-1 (Chinese), 九胜肽-1, Melanostatine, (Met⁵,Pro⁶,D-Phe⁷,D-Trp⁹,Phe¹⁰)-α-MSH (5-13) |
Appearance | White to off-white crystalline powder (solid form); colorless to pale yellow clear solution (liquid form) |
Purity (HPLC) | ≥ 95.0% – 99.99% (cosmetic grade ≥ 98.0% typical; pharmaceutical grade up to 99.99%) |
Peptide Content | ≥ 80.0% |
Water Content (Karl Fischer) | ≤ 8.0% |
Acetic Acid Content (HPLC) | ≤ 15.0% |
TFA Content (HPLC) | ≤ 0.5% |
pH (1% aqueous solution) | 4.5 – 7.5 (optimal: 5.5 – 6.5) |
Density | 1.38 ± 0.1 g/cm³ (predicted) |
Melting Point | >120°C (decomposes) |
Refractive Index (20°C) | 1.3347 – 1.3377 (solution form) |
pKa | 13.32 ± 0.46 (predicted) |
Solubility | Soluble in water (>5 mg/mL at 25°C; ≥0.1 g/mL per some specifications); soluble in glycerin, propylene glycol, DMSO (255 mg/mL), and PBS (pH 7.2) |
InChI Key | KNFLNGRLKALWRF-LDXSYGEZSA-N |
Isomeric SMILES | CSCCC@HC(=O)N1CCC[C@H]1C(=O)NC@HC(=O)NC@@HC(=O)NC@HC(=O)NC@@HC(=O)NC@@HC(=O)N1CCC[C@H]1C(=O)NC@@HC(N)=O |
Heavy Metals | Compliant with global cosmetic safety standards |
TAMC (Total Aerobic Microbial Count) | < 100 CFU/ml |
Pathogens | Absent |
Mechanism of Action
Nonapeptide-1 exerts its skin lightening and whitening effects through a well-characterized biomimetic mechanism that targets the earliest step in the melanogenesis pathway.
1. MC1R Antagonism (Primary Mechanism):
Melanin synthesis begins when α-melanocyte stimulating hormone (α-MSH), a natural tridecapeptide produced in the pituitary gland and keratinocytes, binds to the melanocortin-1 receptor (MC1R) on the surface of melanocytes. This binding activates adenylyl cyclase via a Gs protein-coupled signaling cascade, leading to increased intracellular cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP then triggers the cAMP-dependent protein kinase A (PKA) pathway, which phosphorylates and activates the microphthalmia-associated transcription factor (MITF).
2. cAMP and Melanosome Dispersion Inhibition:
Nonapeptide-1 potently inhibits α-MSH-induced intracellular cAMP accumulation in melanocytes with an IC₅₀ of 2.5 nM, and blocks α-MSH-induced melanosome dispersion with an IC₅₀ of 11 nM. This dual inhibition at both the signaling and organelle transport levels ensures comprehensive suppression of melanin production.
3. Downregulation of Melanogenic Enzymes:
At the molecular level, Nonapeptide-1 (20 μΜ, 3 days) downregulates the expression of MC1R, tyrosinase, TRP-1, TRP-2, and MITF via competitive binding to MC1R in both human epidermal melanocytes (HEM cells) and HaCaT cells. This transcriptional regulation reduces the cellular machinery required for melanin synthesis.
Key Pharmacological Parameters:
Parameter | Value |
|---|---|
MC1R binding affinity (Ki) | 40 nM (selective antagonist) |
MC3R binding affinity (Ki) | 0.47 μM |
MC4R binding affinity (Ki) | 1.34 μM |
MC5R binding affinity (Ki) | 2.4 μM |
cAMP inhibition (IC₅₀) | 2.5 nM |
Melanosome dispersion inhibition (IC₅₀) | 11 nM |
Melanin synthesis inhibition (α-MSH-induced) | 33% |
Key Benefits
Benefit Category | Description |
|---|---|
Skin Brightening | Reduces melanin synthesis at the molecular level by blocking α-MSH from binding to MC1R, resulting in visibly brighter and more radiant skin |
Hyperpigmentation Reduction | Diminishes the appearance of age spots, freckles, sunspots, melasma, and post-inflammatory hyperpigmentation (PIH) |
Even Skin Tone | Promotes uniform complexion by reducing uneven pigmentation and discoloration |
Collagen Synthesis Stimulation | Promotes collagen synthesis, enhancing skin elasticity and reducing the appearance of fine lines and wrinkles |
Anti-Aging | Provides dual anti-aging benefits through both pigmentation control and collagen support |
Safe for Sensitive Skin | Non-cytotoxic; does not affect normal melanocyte function or viability; low irritation potential |
UV Protection Support | Reverses UVA-induced melanin increase, offering potential protective benefits against photoaging |
Non-Mutagenic | Exhibits no mutagenic or toxic effects on cells |
Clinical studies have shown that Nonapeptide-1 has good whitening efficacy on Asian skin types, is non-cytotoxic, and does not affect the function of melanocytes, making it an ideal skin whitening agent.
Applications & Usage Guidelines
Recommended Applications:
Category | Specific Products |
|---|---|
Skin Brightening | Whitening serums, brightening creams, spot correctors, pigment-reducing formulations |
Anti-Aging Face Care | Anti-aging serums, firming creams, daily moisturizers, facial masks, toners, lotions |
Hyperpigmentation Treatment | Freckle removal creams, age spot correctors, melasma treatment products, post-inflammatory hyperpigmentation (PIH) formulations |
Sun Care | Sunscreens, BB creams, CC creams, after-sun repair products |
Makeup | Brightening foundations, illuminating powders, primer formulations |
Eye Care | Eye creams, eye serums (for periorbital hyperpigmentation/dark circles) |
Hair Care | Hair conditioning products (as per IECIC registration) |
Sensitive Skin Care | Gentle brightening products for reactive skin types |
Recommended Concentration:
Form | Recommended Dosage in Final Formulation |
|---|---|
Powder (98%+ purity) | 5 – 5,000 ppm (0.0005% – 0.5%) |
Powder (typical whitening) | 10 – 200 ppm (0.001% – 0.02%) |
Powder (commercial anti-aging) | 0.5% – 3% (5,000 – 30,000 ppm) |
Solution (e.g., 1000 ppm stock) | 1% – 10% |
Solution (0.1% stock) | As supplied |
Gebiotide® Nonapeptide-1 Solution | 1% – 4% |
Maximum historical use (China IECIC) | Leave-on products: 2%; Eye area leave-on: 2% |
Formulation Guidelines
pH Stability: Nonapeptide-1 is stable in cosmetic formulations within the pH range of 4.5–7.5, with optimal stability between pH 5.5 and 6.5. For maximum efficacy, formulations should maintain pH between 6 and 8. Under strongly acidic conditions (pH < 4.0) or strongly alkaline conditions (pH > 8.0), the peptide bond is susceptible to hydrolysis, leading to degradation and loss of activity.
Thermal Stability: Nonapeptide-1 is heat-sensitive and should be added to formulations after the temperature has dropped below 40°C (104°F) during the manufacturing process. Avoid prolonged exposure to temperatures exceeding 50°C. For solution formulations, the addition temperature should be below 45°C.