A nine-amino-acid cosmetic peptide, nonapeptide-1, that blocks the skin's tanning receptor and is sold in brightening creams.
Also called Nonapeptide-1, Melanostatine-5, Melanostatine 5, Melanostatin-5, 153N-6, White 05, Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2
When Melanostatin (Nonapeptide-1)'s status or evidence changes, it's in the next morning's email.
Nonapeptide-1, sold as Melanostatine-5, is a lab-made copy of part of alpha-MSH, the hormone that tells pigment cells to make melanin. Two of its amino acids are swapped for mirror-image (D-) forms, which turns it from an activator into a blocker. It sits on MC1R, the receptor alpha-MSH uses, so the signal to make more pigment is weaker. That makes it the opposite of Melanotan-1 and Melanotan-2, which switch the same receptor on.
Yale researchers found the sequence in 1994 by screening a library of alpha-MSH fragments; it blocked the receptor's response at about 11 nM in lab assays. Later work showed it binds MC1R far more tightly than the related receptors MC3R, MC4R and MC5R. Cosmetic suppliers sell it for dark spots and uneven skin tone.
Human evidence is thin. The only published trial is a 46-person study in India that used a cream combining nonapeptide-1 with phenylethyl resorcinol, other lightening agents and sunscreen to keep melasma from coming back; it did not lower melanin readings significantly more than sunscreen alone. No trial has tested nonapeptide-1 by itself. The name is also confusing: melanostatin is also the name of a different molecule, MIF-1, a three-amino-acid peptide (Pro-Leu-Gly-NH2).
What it binds to, and what happens inside the body after that, step by step.
UV light raises alpha-MSH, which binds MC1R on melanocytes, raises the messenger cAMP and switches on the genes for tyrosinase and other melanin enzymes. Nonapeptide-1 binds MC1R without activating it, so alpha-MSH cannot. In lab assays it blocked alpha-MSH-driven cAMP and pigment dispersion in pigment cells at nanomolar concentrations. Whether enough crosses human skin from a cream to block MC1R is not established.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
The receptor pharmacology is solid: lab studies show nonapeptide-1 blocks MC1R selectively at nanomolar concentrations. In people, the only published trial used it inside a multi-ingredient melasma cream and found no significant melanin difference from sunscreen alone. No study has tested nonapeptide-1 by itself in human skin.
46 people with melasma in India, 23 per group, after 8 weeks of triple-combination cream
A cream with phenylethyl resorcinol, nonapeptide-1, aminoethyl phosphinic acid, antioxidants and sunscreen kept melasma scores falling while they rose with sunscreen alone, but the severity and melanin index differences were not statistically significant.
Read the studyPeptide library of 31,360 alpha-MSH 5-13 analogs screened in pigment-cell receptor assays
Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2 was the most potent antagonist, with an IC50 of 11 nM; D-Trp and Phe were essential for blocking.
Read the studyCells expressing human MC1, MC3, MC4 and MC5 receptors
153N-6, the same peptide, was selective for the MC1 receptor.
Read the studyHuman keratinocytes (HaCaT) and human epidermal melanocytes exposed to UVA
Used nonapeptide-1 acetate as a comparison MC1R blocker in UVA-stressed skin cells; a supplier summary of this work reports it lowered melanin and MC1R, tyrosinase and MITF at 20 micromolar over 3 days.
Read the studyCell studies plus an in vivo model not described in the abstract
Nonapeptide-1 was attached to silica nanoparticles carrying green tea EGCG; the combination inhibited melanin 5.22 times more than free EGCG.
Read the studyWhen a new Melanostatin (Nonapeptide-1) study in people is published, the daily email covers it.
These are questions the published research has not answered.
No product containing Melanostatin (Nonapeptide-1) is approved as a medicine by the FDA.
Sold only as a cosmetic ingredient, which FDA does not review for efficacy before sale. It has never been developed as a drug, and we found no published safety assessment by the US Cosmetic Ingredient Review panel as of October 2026. Not named on the WADA list. Do not confuse it with melanostatin in the older sense, MIF-1 (Pro-Leu-Gly-NH2), a different tripeptide.
When the FDA or WADA changes Melanostatin (Nonapeptide-1)'s status, it's in the next morning's email.
No human half-life has been published for Melanostatin (Nonapeptide-1), so we do not draw a clearance curve. Half-lives quoted online for it are usually estimates from animal data.
No human study or approved label has published a dose for Melanostatin (Nonapeptide-1), so there is no table to show.
No dose of Melanostatin (Nonapeptide-1) has been tested in a published human study or approved on a label. Numbers that circulate online come from animal studies scaled up by guesswork or from sellers. We do not reproduce them.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
Tap a claim to see what the studies found.
Nonapeptide-1 is synthetic, built from a fragment of alpha-MSH with two mirror-image amino acids. The peptide listed under the plain name melanostatin is MIF-1, a different three-amino-acid molecule.
At the receptor level, yes: Melanotan peptides switch MC1R on, and nonapeptide-1 blocks it. Whether a cream blocks MC1R enough in people to matter is unproven.
It has never been tested alone. The one trial used a multi-ingredient cream and did not beat sunscreen on melanin readings.
Blocking MC1R reduces the signal to make new melanin. It does not break down pigment already in the skin.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
Brightening serums pair an MC1R blocker with tyrosinase inhibitors such as glutathione or phenylethyl resorcinol to hit two steps of melanin production.
EvidenceThe only trial of a nonapeptide-1 combination did not beat sunscreen on melanin readings. No study has tested nonapeptide-1 with glutathione.
Sold mainly as a cosmetic ingredient; a research-chemical datasheet lists powder storage sealed and away from light and moisture at -20 C for 1 year or -80 C for 2 years.
Follow the cosmetic product's packaging and expiry date; no independent stability data are published.
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