Palmitoyl pentapeptide-4
Signal peptide (cosmetic ingredient)
Status
Cosmetic ingredient
A cosmetic skin-conditioning ingredient, not an approved drug; the US Cosmetic Ingredient Review panel concluded in 2024 that it is safe as used in cosmetics, and FDA treats products claiming to change skin structure or function as drugs.
Evidence
Preliminary
One company-run split-face RCT in 93 women and a few small trials; no large independent studies.
Palmitoyl pentapeptide-4 (Matrixyl) is a five-amino-acid fragment of a collagen precursor with a fatty acid attached, used in anti-wrinkle creams. It is a cosmetic ingredient, not a drug, and its evidence rests on small, mostly manufacturer-run trials.
Structure
5 residuesPoint at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.
Sequence as text
Pal-K-T-T-K-S-OH
What it is used for
- Fine lines and wrinkles in cosmetic creams, in small trials (studied)
- Skin firmness and general anti-ageing (claimed, unproven)
How it works
KTTKS is a fragment of type I procollagen; in fibroblast cultures this pentapeptide stimulated production of extracellular matrix proteins, including collagen (Katayama 1993). The attached palmitic acid, a 16-carbon fatty acid, makes it more fat-soluble and more stable against skin enzymes than plain KTTKS. In lab tests on hairless mouse skin, about 15% of applied Pal-KTTKS was retained in the skin, mostly in the outer layers, with only 0.6% reaching the dermis.
How strong the evidence is
Preliminary
In a 12-week, double-blind, placebo-controlled, split-face study in 93 women aged 35 to 55 (Robinson 2005, by Procter & Gamble scientists), a moisturiser with 3 ppm Pal-KTTKS reduced wrinkles and fine lines on image analysis compared with the same moisturiser alone. A 2023 double-blind trial in 21 Indonesian women over 8 weeks found modest improvement in crow's feet, better than acetyl hexapeptide-3 and placebo. The underlying lab rationale comes from fibroblast studies (Katayama 1993). There are no large independent trials.
Risks and side effects
- Judged safe as used in cosmetics by the CIR panel, which reviewed irritation, sensitisation and genotoxicity data; leave-on products use it at up to about 0.001%.
- Effects, where present, are modest and cosmetic; how much reaches the deeper skin is uncertain.
- Products marketed with drug-like claims to rebuild collagen fall outside cosmetic rules and may be unapproved drugs in the US.
Regulatory status
Status by country
| Jurisdiction | Status | Source |
|---|---|---|
| USUnited States | Cosmetic ingredient | Source 2 |
| EUEuropean Union | Cosmetic ingredient | Source 9 |
| UKUnited Kingdom | No authorised medicine | Source 10 |
| AUAustralia | Cosmetic ingredient | Source 11 |
| CACanada | No authorised medicine | Source 12 |
Sources
- 01PubChem Compound Summary: Palmitoyl Pentapeptide-4 (CID 9897237)(opens the source in a new tab)
- 02Safety Assessment of Myristoyl Pentapeptide-4, Palmitoyl Pentapeptide-4, and Pentapeptide-4 as Used in Cosmetics (Final Report)(opens the source in a new tab)
- 03Safety Assessment of Tripeptide-1, Hexapeptide-12, their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics (Final Report)(opens the source in a new tab)
- 04Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin(opens the source in a new tab)
- 05A pentapeptide from type I procollagen promotes extracellular matrix production(opens the source in a new tab)
- 06Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet(opens the source in a new tab)
- 07Peptides and Growth Factors in Cosmetics: Are They Banned?(opens the source in a new tab)
- 08Is It a Cosmetic, a Drug, or Both? (Or Is It Soap?)(opens the source in a new tab)
- 09CosIng: PALMITOYL PENTAPEPTIDE-4(opens the source in a new tab)
- 10MHRA Products: active substances beginning with P(opens the source in a new tab)
- 11Australian Inventory of Industrial Chemicals: L-Serine, N2-(1-oxohexadecyl)-L-lysyl-L-threonyl-L-threonyl-L-lysyl- (CAS 214047-00-4)(opens the source in a new tab)
- 12Drug Product Database online query(opens the source in a new tab)
Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.