# Decapeptide-12

> Decapeptide-12 is a synthetic ten-residue peptide, Tyr-Arg-Ser-Arg-Lys-Tyr-Ser-Ser-Trp-Tyr, studied as a tyrosinase inhibitor for skin hyperpigmentation. It has the formula C65H90N18O17 and a molecular weight of 1395.5 g/mol. Small clinical studies have evaluated it in melasma, photodamage-related pigmentation and post-inflammatory hyperpigmentation, mostly within multi-product regimens. It is a cosmetic ingredient, not an FDA-approved drug.

Canonical: https://peptideproperties.com/compounds/decapeptide-12/

## Identity

- **Class:** Copper & Cosmetic Peptides
- **Molecular formula:** C65H90N18O17
- **Molecular weight:** 1395.5 g/mol
- **Monoisotopic mass:** 1394.6731 Da
- **CAS number:** 137665-91-9
- **PubChem CID:** 25087629
- **InChIKey:** OYVFAMLECFSFEI-UHFFFAOYSA-N
- **Sequence:** YRSRKYSSWY
- **Sequence notes:** Unmodified linear peptide with a free N-terminal amine and free C-terminal carboxylic acid; the PubChem record does not specify stereochemistry. A palmitoylated derivative has been made experimentally.

## Key facts

- Class: synthetic oligopeptide; cosmetic skin-brightening ingredient
- Sequence: ten standard residues, YRSRKYSSWY, with free N- and C-termini
- Formula C65H90N18O17; molecular weight 1395.5 g/mol (PubChem CID 25087629)
- CAS 137665-91-9
- Studied mechanism: competitive inhibition of mushroom and human tyrosinase
- Evidence base: small pilot and open-label clinical studies plus in-vitro skin permeation work
- Regulatory status: not an FDA-approved drug; used as a cosmetic ingredient

## What Is Decapeptide-12?

Decapeptide-12 is a synthetic linear peptide of ten amino acids that has been studied as a tyrosinase inhibitor for reducing skin hyperpigmentation. Tyrosinase is the enzyme that drives melanin production, and the peptide is used as a skin-brightening ingredient in cosmetic formulations.A 2009 pilot study described the oligopeptide, identified in that abstract by a trade name that PubChem lists as a synonym of decapeptide-12, as a competitive inhibitor of mushroom and human tyrosinase that lacked the toxicity associated with hydroquinone.[1] A 2021 paper summarized it as safer than hydroquinone in reducing melanin content, with reported efficacy of more than 50% after 16 weeks of treatment.[2]Most clinical data come from small studies in which decapeptide-12 was part of a regimen that also included a cleanser, a glycolic acid product and sunscreen.[3][4] Study populations have spanned Fitzpatrick skin types I through IV, including Hispanic women with melasma.

## Chemical Structure and Molecular Identity

Decapeptide-12 has the sequence Tyr-Arg-Ser-Arg-Lys-Tyr-Ser-Ser-Trp-Tyr (YRSRKYSSWY), with a free N-terminal amine and a free C-terminal carboxylic acid. PubChem (CID 25087629) lists the molecular formula C65H90N18O17 and a molecular weight of 1395.5 g/mol.The sequence is rich in aromatic residues, with three tyrosines and one tryptophan, and carries three basic residues, two arginines and a lysine. Three serines add further polarity. The molecule is strongly hydrophilic, with a computed XLogP of -6.5 in PubChem.
### Key identifiers

- CAS number: 137665-91-9
- InChIKey: OYVFAMLECFSFEI-UHFFFAOYSA-N
- PubChem CID: 25087629
- Residues: 10 (Tyr x3, Ser x3, Arg x2, Lys x1, Trp x1)Its size and polarity matter for topical use. Researchers have noted that decapeptide-12 suffers from limited transcutaneous penetration because of its hydrophilicity and high molecular weight, and they synthesized a palmitoylated version to make it more lipophilic.[2]

## Research History and Development

Decapeptide-12 was developed as a hydroquinone alternative and moved quickly from enzyme studies into small dermatology trials. By 2009, it had already been shown to competitively inhibit mushroom and human tyrosinase, and that year a placebo-controlled pilot study tested it in recalcitrant melasma.[1]Between 2012 and 2014, investigators studied it as part of a multi-step skin-brightening system. An open-label study evaluated the system in facial hyperpigmentation from chronic photodamage,[3] and a multicenter open-label study tested it in Hispanic women with melasma after earlier studies in Caucasian and Asian volunteers.[4] A 2014 report examined combining topical delivery with dermal infusion for post-inflammatory hyperpigmentation in skin of color.[5]More recent work has focused on delivery. A 2021 study compared native and palmitoylated decapeptide-12 in human skin permeation experiments using chemical penetration enhancers and microneedles.[2]

## Mechanisms Studied in Research

The main mechanism studied for decapeptide-12 is inhibition of tyrosinase, the enzyme that drives melanin synthesis. Studies describe it as a competitive inhibitor of both mushroom and human tyrosinase.[1]Clinical investigators summarize its mechanism as inhibition of melanin synthesis through tyrosinase inhibition. They also list a low incidence of side effects and a lack of cytotoxicity as features of the peptide, based on its development data.[3]
### Docking of native and modified peptide
In the 2021 delivery study, molecular docking indicated that native decapeptide-12 and its palmitoylated derivative showed similar predicted activity toward tyrosinase, suggesting that adding the fatty acid chain need not disrupt the enzyme interaction.[2] This was a computational comparison, not an enzyme assay.
### Delivery as a limiting step
For a topically applied peptide, crossing the stratum corneum is a prerequisite for reaching pigment-producing cells. The same study reported that the native peptide's skin permeation increased with a microneedle patch but not with chemical penetration enhancers, while the palmitoylated version achieved the best skin retention.[2]

## Key Findings From Published Studies

Clinical findings for decapeptide-12 come from one five-person placebo-controlled pilot and several open-label studies of combination regimens, supported by in-vitro skin permeation work. All of the clinical studies were small.
### Split-face pilot in recalcitrant melasma (2009)
In a split-face, randomized, double-blind, placebo-controlled pilot, five women with Fitzpatrick phototype IV and moderate recalcitrant melasma were treated for 16 weeks. Outcomes were rated on 10-point and five-point grading scales. Treatment was well tolerated with no visible irritation or allergy, and all five showed statistically significant improvement in the appearance of melasma and overall facial aesthetics, with high satisfaction.[1]
### Photodamage-related hyperpigmentation (2012)
Fifteen women with Fitzpatrick skin types I to IV and documented photodamage used decapeptide-12 with an antioxidant cleanser, a glycolic acid moisturizer and broad-spectrum sunscreen; 13 completed the study. At 24 weeks, 38.5% moved from moderate (grade 3) photodamage to completely cleared (grade 1), and a further 30.7% improved from moderate to mild. Among participants who started with severe (grade 4) photodamage, 15.4% of the cohort improved to moderate and another 15.4% to mild. All treatments were well tolerated.[3]
### Melasma in Hispanic women (2013)
In an open-label multicenter study of 33 Hispanic women with mild-to-moderate melasma, a regimen of decapeptide-12 cream, antioxidant cleanser, buffered glycolic acid lotion and SPF 30 sunscreen produced mean Melasma Area and Severity Index (MASI) reductions of 36%, 46%, 54% and 60% at weeks 4, 8, 12 and 16, and standardized clinical photography showed a visible reduction in melasma. The system was well tolerated in participant self-assessments, and no adverse events were reported.[4]
### Post-inflammatory hyperpigmentation (2014)
A 2014 report on combining topical delivery with dermal infusion of decapeptide-12 for post-inflammatory hyperpigmentation in skin of color is indexed in PubMed without an abstract. Its title states that the combination accelerated resolution of the pigmentation, but outcome data are not available in the PubMed record.[5]
### Skin permeation (in vitro, 2021)
In human skin permeation tests, the palmitoylated peptide showed the best skin retention, and its permeation was enhanced by oleic acid and menthol. The authors estimated that cutaneous absorption of the palmitoylated form reached a therapeutic concentration within skin.[2]Because synthesis can leave deletion or truncation impurities, researchers typically verify decapeptide-12 identity and purity with HPLC and mass spectrometry certificates of analysis.Because synthesis can leave deletion or truncation impurities, researchers typically verify decapeptide-12 identity and purity with HPLC and mass spectrometry certificates of analysis.

## Regulatory and Research Status

Decapeptide-12 is not an FDA-approved drug. It is used as a cosmetic skin-brightening ingredient and has not completed drug-development trials.The clinical evidence has clear limits. The only placebo-controlled study enrolled five participants,[1] and the larger studies were open-label and combined decapeptide-12 with glycolic acid, an antioxidant cleanser and sunscreen, so its individual contribution cannot be separated.[3][4] Some favorable statements about safety and cytotoxicity come from investigators summarizing development data rather than from independent comparative trials.[3]
### Evidence at a glance
StudyDesignParticipants or modelPeptide isolated?Melasma pilot (2009)Split-face, randomized, double-blind, placebo-controlled5 women, phototype IVYesPhotodamage (2012)Open-label15 women enrolled, 13 completedNo, multi-product systemMelasma (2013)Open-label, multicenter33 Hispanic womenNo, multi-product systemSkin permeation (2021)In vitroHuman skin samplesYes, native and palmitoylated formsOpen questions include randomized, vehicle-controlled trials of the peptide alone, direct comparisons with established depigmenting agents in larger groups, and confirmation that topically applied peptide reaches melanocytes in meaningful amounts.[2]

## FAQ

**What is decapeptide-12?**
Decapeptide-12 is a synthetic ten-amino-acid peptide, YRSRKYSSWY, studied as a competitive inhibitor of tyrosinase, the enzyme that drives melanin production. It is used as a cosmetic skin-brightening ingredient. Small clinical studies have tested it in melasma and photodamage-related hyperpigmentation, usually alongside glycolic acid, an antioxidant cleanser and sunscreen.

**What is the molecular weight of decapeptide-12?**
PubChem lists decapeptide-12 (CID 25087629) with a molecular weight of 1395.5 g/mol and the molecular formula C65H90N18O17. Its CAS number is 137665-91-9. The molecule has ten residues, including three tyrosines and a tryptophan, and is strongly hydrophilic, which researchers say limits its passage through skin.

**Is decapeptide-12 FDA approved?**
No. Decapeptide-12 is not an FDA-approved drug. It is used as a cosmetic ingredient for skin brightening. Its clinical evidence consists of a five-person placebo-controlled pilot study and several small open-label studies of multi-product regimens, which is not the level of evidence required for drug approval.

**How does decapeptide-12 work?**
Published studies describe decapeptide-12 as a competitive inhibitor of mushroom and human tyrosinase, the enzyme that drives melanin synthesis. By blocking this enzyme, it is proposed to reduce melanin production. A 2021 docking study found that a palmitoylated version showed similar predicted activity toward tyrosinase as the native peptide.

**How is decapeptide-12 different from hydroquinone?**
Decapeptide-12 is a ten-residue peptide, while hydroquinone is a small phenolic compound. Both target melanin production, but decapeptide-12 was developed as an alternative after studies found it inhibited tyrosinase without the toxicity associated with hydroquinone. No large head-to-head clinical trial comparing the two appears in the indexed literature reviewed here.

**What does the research on decapeptide-12 show?**
In a five-person split-face pilot, all participants with recalcitrant melasma showed significant improvement. In an open-label study of 33 Hispanic women, mean MASI scores fell by 60% at 16 weeks on a regimen including decapeptide-12. These studies were small and mostly combined the peptide with glycolic acid and sunscreen.

## References

1. Hantash BM, Jimenez F. A split-face, double-blind, randomized and placebo-controlled pilot evaluation of a novel oligopeptide for the treatment of recalcitrant melasma. Journal of drugs in dermatology : JDD 2009. PMID: 19663110
2. Chen J, Bian J, Hantash BM, et al. Enhanced skin retention and permeation of a novel peptide via structural modification, chemical enhancement, and microneedles. International journal of pharmaceutics 2021. PMID: 34242628
3. Kassim AT, Hussain M, Goldberg DJ. Open-label evaluation of the skin-brightening efficacy of a skin-brightening system using decapeptide-12. Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology 2012. PMID: 22401652
4. Ramírez SP, Carvajal AC, Salazar JC, et al. Open-label evaluation of a novel skin brightening system containing 0.01% decapeptide-12 in combination with 20% buffered glycolic acid for the treatment of mild to moderate facial melasma. Journal of drugs in dermatology : JDD 2013. PMID: 23839199
5. Bhatia A, Hsu JTs, Hantash BM. Combined topical delivery and dermalinfusion of decapeptide-12 accelerates resolution of post-inflammatory hyperpigmentation in skin of color. Journal of drugs in dermatology : JDD 2014. PMID: 24385124