Matrixyl

pal-KTTKS, palmitoyl pentapeptide-3 (older INCI name), Matrixyl (Sederma trade name), palmitoyl-lysyl-threonyl-threonyl-lysyl-serine

Skin & cosmetic

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Synthetic lipopeptide: a five-amino-acid fragment of type I procollagen (KTTKS) with a palmitic acid tail attached to help it pass through the skin's outer layer
Mechanism: A "matrikine" — a fragment of a matrix protein that signals to fibroblasts to make more collagen, fibronectin and glycosaminoglycans, as if repairing a wound
Routes studied: Topical only (creams and serums). Not studied by injection or orally
Dose range reported: Cosmetic studies and products: roughly 3–8 ppm of the active peptide (the raw material is typically a ~100 ppm solution used at 3–8% of a formula). Study that showed benefit used 3 ppm twice daily for 12 weeks
Half-life: Not applicable in the systemic sense; the peptide is designed to act locally in skin and is broken down by skin enzymes. Penetration to the dermis is limited and debated
Storage: Finished products: room temperature, away from heat and light, as per label. Raw peptide: refrigerate, protect from light
Regulatory status: Permitted cosmetic ingredient worldwide; not a medicine anywhere

Doses are as reported in studies or by the community — never recommendations.

1What it is

Matrixyl is the best known of the "signal peptides" used in anti-ageing skincare. The active part is KTTKS, a five-amino-acid sequence that sits at the end of type I procollagen — the precursor your body makes before it trims it into mature collagen. In 1993 a research group found that this fragment, on its own, told cultured skin fibroblasts to make more collagen (Katayama 1993, J Biol Chem). The French ingredient company Sederma added a palmitoyl (fatty acid) tail to help the water-loving peptide cross the oily outer skin and launched it as Matrixyl around 2000.

It is a synthetic copy of a natural sequence, not something isolated from tissue. The INCI name changed from palmitoyl pentapeptide-3 to palmitoyl pentapeptide-4 in the late 2000s; both names describe the same molecule, which causes confusion when reading older product labels and papers.

2How it's thought to work

When skin is injured, collagen and other matrix proteins are broken down, and the fragments released act as signals ("matrikines") that tell nearby cells repair is needed. KTTKS is proposed to mimic that signal without any injury:

In cultured fibroblasts it increases production of type I and III collagen, fibronectin and glycosaminoglycans (the water-holding molecules of the dermis).

The palmitoyl tail improves penetration through the stratum corneum; studies with skin models show much of the peptide stays in the upper layers and some is broken down by skin proteases before it reaches fibroblasts (Abu Samah & Heard 2011, Int J Pharm; Choi 2014).

Any wrinkle-reducing effect would come from gradual rebuilding of dermal matrix, so visible changes take weeks, not days.

A five-amino-acid fragment of procollagen with a fatty tail to help it through the outer skin layer. Fibroblasts read the fragment as a signal that collagen has been damaged and make more.Schematic — not to scale

The mechanism is well supported in cell culture; how much active peptide actually reaches living dermis from a cream is the open question.

3What the research shows

Graded A (small)

Facial wrinkles and photo-aged skin

A 12-week, double-blind, split-face, placebo-controlled study in 93 women aged 35–55 applied 3 ppm pal-KTTKS in a moisturiser to one side of the face and the vehicle alone to the other, twice daily. Image analysis and expert grading showed small but statistically significant improvements in wrinkle depth, roughness and skin texture on the treated side (Robinson 2005, Int J Cosmet Sci). The study was funded and run by Procter & Gamble, which used the ingredient in its own products. Effects were modest. [2]

Collagen synthesis in cells and skin models

Fibroblast studies show increased collagen, elastin and fibronectin output with KTTKS and pal-KTTKS (Katayama 1993; Jones 2013, Mol Pharm). Ex-vivo human skin work shows the palmitoyl form penetrates better than the bare peptide but is partly degraded in skin (Abu Samah & Heard 2011). [1][3][4]

Comparison with retinoids

Reviews of topical peptides generally place pal-KTTKS as better tolerated than retinoids but with weaker and less consistent evidence (Gorouhi & Maibach 2009, Int J Cosmet Sci; Schagen 2017, Cosmetics). No head-to-head against tretinoin is published. [5][6]

Wound healing, scarring, hair

Occasional community use for scars and in hair serums; no published human data.

4Reported side effects and interactions

Literature-reported

Very well tolerated; no serious adverse events in the trial or in decades of cosmetic use. Rare mild irritation or contact dermatitis, usually attributed to the base formula rather than the peptide.

Community-reported

occasional stinging on freshly exfoliated skin; some report no visible effect. No systemic effects reported.

Theoretical. none specific. Because the peptide is a collagen fragment, immune sensitisation is theoretically possible but has not been reported in practice.

Interactions. no pharmacological interactions. Formulation note: strong acids (low-pH vitamin C, glycolic acid) and copper peptides are often said in community guides to destabilise or compete with signal peptides when layered immediately; evidence for this is weak, but applying at different times of day avoids the question.

Markers researchers commonly monitor

No blood markers are relevant to a topical cosmetic peptide. Members tracking results use: No compound-specific lab monitoring is established.

Marker	Why it's watched
Standardised photographs	same lighting, angle and time of day, every 2–4 weeks; the only honest home measure of fine-line change.
Skin hydration/TEWL meters (if available)	used in the trials; a cheap consumer corneometer gives a rough trend.
Irritation diary	redness or stinging usually points to the formula base, not the peptide.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Topical only. Supplied as a finished cosmetic or as a raw ingredient solution for formulators; there is no vial to and no injectable form. Store finished products as labelled, out of direct sun. Raw material should be refrigerated and protected from light. Injection of cosmetic-grade peptides is never appropriate. The calculator does not apply to this entry.

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6Commonly studied alongside

Matrixyl 3000 (#112), Argireline (#50), GHK-Cu (#5, topical context), retinoids, vitamin C, niacinamide — the usual "peptide plus retinoid at night, vitamin C in the morning" routine seen in community guides.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Permitted cosmetic ingredient; no FDA approval required or sought for cosmetics. Claims about "repairing" skin structure fall under FDA cosmetic-vs-drug rules
European Union	Permitted under the Cosmetics Regulation (EC 1223/2009); listed in CosIng
United Kingdom	Same as EU under UK cosmetics regulations
Australia	Cosmetic ingredient; not a therapeutic good
South Africa	Cosmetic ingredient; not registered as a medicine
Sport	Not listed by WADA; topical cosmetic use raises no anti-doping issue

8Open questions

How much intact pal-KTTKS reaches the dermis from a cream, and does the effect depend on that or on signalling in the epidermis?
Independent, non-industry replication of the 2005 trial has not been published.
Optimal concentration: the active is used at a few ppm, and whether more is better is untested.
Durability of benefit after stopping.

9References

1Katayama K et al. (1993). A pentapeptide from type I procollagen promotes extracellular matrix production. J Biol Chem. PubMed
2Robinson LR et al. (2005). Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. Int J Cosmet Sci. PubMed · DOI
3Abu Samah NH, Heard CM (2011). Topically applied KTTKS: a review. Int J Cosmet Sci. DOI
4Jones RR et al. (2013). Collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts. Mol Pharm. PubMed · DOI
5Gorouhi F, Maibach HI (2009). Role of topical peptides in preventing or treating aged skin. Int J Cosmet Sci. PubMed · DOI
6Schagen SK (2017). Topical peptide treatments with effective anti-aging results. Cosmetics. DOI
7Lintner K, Peschard O (2000). Biologically active peptides: from a laboratory bench curiosity to a functional skin care product. Int J Cosmet Sci. PubMed · DOI

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

26 Oct 2026Profile published — awaiting medical review

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