Nonapeptide-1 (INCI name), Melanostatine 5, 153N-6
A synthetic nine-amino-acid peptide built on part of alpha-MSH, the hormone that tells pigment cells to tan, designed to block alpha-MSH’s receptor (MC1R) instead of switching it on. It’s sold in brightening serums to fade dark patches.
None of these uses is approved. Uses tested in people come first, then claims that rest on animal studies or user reports.
Trial: tested in people, with the result. Animal: cell or animal studies only. No study: nothing published supports it.
Every compound’s uses, by body system: evidence map, and by condition: conditions A to Z.
Category 2 is FDA’s list of bulk substances that may present significant safety risks in compounding. The 503A bulks list adds substances that pharmacies may compound with. Advisory committee votes are advice; FDA makes the final decision. Sport status follows the WADA Prohibited List in force since January 1, 2026; athletes should confirm with their anti-doping organization. Checked October 5, 2026. Status outside the US checked October 7, 2026 against EMA, MHRA, Health Canada and TGA records. By country: EU, UK, Canada, Australia. Status of every compound.
Nonapeptide-1 blocks MC1R, the receptor on pigment cells that alpha-MSH switches on to make dark melanin. It was found in 1994 by screening peptides built on part of alpha-MSH, and it blocked alpha-MSH’s effect on frog pigment cells at very low concentrations; it binds the human MC1 receptor far more than the related MC3, MC4 and MC5 receptors. In human pigment cells it lowered melanin, including after UVA light.
AnimalMainly from cell and animal studies; not shown in people.
Whether enough of this large peptide crosses skin to block MC1R in pigment cells is unknown, as is its own effect in people apart from the other lightening agents it was tested with.
Shen 2025
Essence listing 3% nonapeptide-1 with 0.5% arbutin, 3% glabridin and Cordyceps extract, alongside tranexamic acid tablets, for 12 weeks.
Chatterjee 2021
Cream with phenylethyl resorcinol, nonapeptide-1, other actives and sunscreen, used after 8 weeks of a hydroquinone triple-combination cream.
Continuous, shown over 26 weeks
The ways Nonapeptide-1 is most often run, each tagged with where it comes from.
Shen 2025, 62 women with melasma, all also taking tranexamic acid tablets: as good as hydroquinone cream, with fewer side effects (1 of 30 vs 4 of 29).
Chatterjee 2021, 46 people after 8 weeks of triple-combination cream: melasma kept improving on it but not significantly more than on sunscreen alone.
Applied to dark patches or the whole face. Topical only; never inject it.
Nothing special. Skip it and use the next application as usual.
With tranexamic acid tablets, melasma scores and melanin readings fell as much with an essence containing it as with hydroquinone cream (Shen 2025).
TrialIt lowered melanin in human pigment cells and blunted the rise after UVA light; no study shows the same in skin.
AnimalItching (1 of 30 on an essence containing it, cleared in a day)
Patch-test first. Stop if it doesn’t settle.
Eye irritation
Keep it out of the eyes. Rinse with water if it gets in.
Infection or harm from injecting a cosmetic product
Never inject topical products; they aren’t sterile.
Stop and see a doctor for a spreading rash, swelling, blistering or hives, eye pain after contact, or any dark spot that grows, bleeds or changes.
The side effects people ask about most, answered one by one. Each answer says where it comes from.
Trial: reported in human studies. Precaution: a concern that follows from how it works or from a related drug, not measured. Not reported: studied in people and not reported. A side effect that hasn’t been reported can still happen, especially with long or high-dose use. Any of these across every compound: the side-effect finder.
No product label covers nonapeptide-1, so these come from human studies and from precautions based on how it works. Most important first.
Precaution: follows from how it works or from a related drug, and hasn’t been tested. This isn’t a complete list: a pharmacist or doctor can check a specific medicine or condition. Every documented interaction, by medicine: drug interactions.
What’s known about pregnancy, breastfeeding, kidney and liver problems, age and surgery. Where nothing has been studied, the row says so.
Precaution: not studied, so the caution follows from how it works or from a related drug. Ages are given as approved or studied; this site never gives doses for children. Across every compound: pregnancy, breastfeeding, kidney disease, liver disease, older adults and surgery.
Usually run on its own.
2 key published human studies, with how many people took part. Animal studies aren’t listed here.
Melasma scores (MASI), melanin and redness readings fell in both groups with no difference between them; side effects in 1 of 30 on the essence (itching) vs 4 of 29 on hydroquinone (redness, tingling).
Shen et al., J Cosmet Dermatol 2025, PMID 40590148
Melasma severity and melanin index improved more on the combination, but not significantly; MASI kept falling on it and rose on sunscreen alone.
Chatterjee et al., Indian J Dermatol Venereol Leprol 2021, PMID 34379946
No ongoing trial of nonapeptide-1 is registered, and none has finished recently without publishing its results. Checked on ClinicalTrials.gov, October 7, 2026. Every compound: trials under way.
Human data are two randomized trials of products mixing it with other lightening agents (62 women for 12 weeks and 46 people over about 8 months), so its own effect can’t be separated, and one found no significant benefit over sunscreen. Its MC1R-blocking action comes from frog-cell, human cell and receptor-binding studies; skin penetration hasn’t been measured, and long-term use is untested.
Nonapeptide-1 is used on the skin, so the math is a dilution, not a syringe dose.
| Powder | Serum volume | Strength | Percent | ppm |
|---|---|---|---|---|
| 10 mg | 100 mL | 0.1 mg/mL | 0.01% | 100 ppm |
| 10 mg | 200 mL | 0.05 mg/mL | 0.005% | 50 ppm |
| 10 mg | 500 mL | 0.02 mg/mL | 0.002% | 20 ppm |
| 10 mg | 1,000 mL | 0.01 mg/mL | 0.001% | 10 ppm |
Ingredient makers sell it as a dilute solution in water, butylene glycol and dextran, and its peptide content isn’t published; trial products list it only by percent of that solution. The table shows only the arithmetic: 10 mg in 200 mL of serum gives 50 ppm.
Every compound side by side: the half-life chart and the storage chart.
Every compound’s numbers: the identifiers table.
Ingredient makers supply a dilute solution in water, butylene glycol and dextran with unpublished peptide content, so “3% nonapeptide-1” on a label doesn’t mean 3% peptide. Reagent-grade powder is also sold, often as an acetate salt.
A synthetic nine-amino-acid peptide built on part of alpha-MSH, the hormone that tells pigment cells to tan, designed to block alpha-MSH’s receptor (MC1R) instead of switching it on. It’s sold in brightening serums to fade dark patches.
Nonapeptide-1 blocks MC1R, the receptor on pigment cells that alpha-MSH switches on to make dark melanin. It was found in 1994 by screening peptides built on part of alpha-MSH, and it blocked alpha-MSH’s effect on frog pigment cells at very low concentrations; it binds the human MC1 receptor far more than the related MC3, MC4 and MC5 receptors. In human pigment cells it lowered melanin, including after UVA light. Whether enough of this large peptide crosses skin to block MC1R in pigment cells is unknown, as is its own effect in people apart from the other lightening agents it was tested with.
Not approved as a drug in the US or EU; used as a cosmetic ingredient. Cosmetics don’t need FDA approval before sale. Never nominated for FDA’s compounding bulk lists; it isn’t on any of FDA’s 503A or 503B category lists (May 2026 and March 2025 versions).
From human studies (Shen 2025): Essence listing 3% nonapeptide-1 with 0.5% arbutin, 3% glabridin and Cordyceps extract, alongside tranexamic acid tablets, for 12 weeks. Chatterjee 2021: Cream with phenylethyl resorcinol, nonapeptide-1, other actives and sunscreen, used after 8 weeks of a hydroquinone triple-combination cream. These are the amounts sources reference, not recommendations.
No product label covers nonapeptide-1, so these come from human studies and from precautions based on how it works. Anyone thinking of injecting it: It is a cosmetic ingredient, not made to injectable standards, and has never been tested by injection; it acts on the receptor family Melanotan targets. People with a changing or irregular dark spot: A fading product can delay the skin check a changing pigmented spot needs; the trials enrolled only people with diagnosed melasma. Pregnancy or breastfeeding: No human safety data exist; pregnant and breastfeeding women were excluded from the 62-woman trial.
Before mixing: Freezer (about −20 °C), dry and away from light. After mixing: Finished serum: as labeled, cool and dark. This is common practice; no product label covers it.
No. Not named on the 2026 list. It’s a topical cosmetic ingredient, not a drug of the kind S0 covers. The 2027 list adds peptides to S0’s examples but names no cosmetic ingredients.
Yes. The human studies section lists 2 published studies. The largest, from 2025, included 62 people. Melasma scores (MASI), melanin and redness readings fell in both groups with no difference between them; side effects in 1 of 30 on the essence (itching) vs 4 of 29 on hydroquinone (redness, tingling).
Trial An 8-month, three-phase maintenance trial in 46 people, part of it on a product containing it; 12 weeks in 62 women in the other trial.
No study Used in serums and creams, but skin penetration hasn’t been measured. A nanoparticle carrier for it has been tested only in lab and mouse work, and injection is untested.
No study There’s no label and no overdose data, and cosmetic products contain small amounts. Call Poison Help (1-800-222-1222), or emergency services for severe symptoms.
For uses, the side-effect questions, special situations, trials, identifiers and status outside the US