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Research and educational purposes only. This library summarises published research and regulatory status. It is not medical advice, not a recommendation to use any compound, and not a substitute for a licensed professional. Intended for adults.

Library

Matrixyl

Topical cosmetic signal peptide (matrikine)

Also known as: palmitoyl pentapeptide-4, pal-KTTKS, palmitoyl pentapeptide-3, pal-KTTKS matrikine, Matrixyl (pal-KTTKS)

Evidence level: Clinical research

What it is

Matrixyl (pal-KTTKS) is a topical cosmetic peptide best known for reducing the look of fine lines and wrinkles, found in many anti-aging serums and creams. It's a short collagen-derived 'signal peptide' attached to a fatty tail so it can penetrate skin — the collagen fragment is thought to signal skin cells to make more collagen. It is a cosmetic ingredient, not an FDA-approved drug, and it isn't injected.

What the research found

Matrixyl (palmitoyl pentapeptide, pal-KTTKS) is a cosmetic anti-aging peptide with some of the better human evidence among cosmetic peptides. In a 12-week randomized, double-blind, placebo-controlled split-face study of 93 women, a moisturizer containing 3 ppm pal-KTTKS produced significant improvement in fine lines and wrinkles versus the same moisturizer without it, and was well tolerated. A separate lab study showed the palmitoyl tail matters — it helped the peptide penetrate skin layers the unmodified version did not. The evidence is real but modest: a single well-run cosmetic trial, not drug-level proof.

Status and regulatory position

Not a drug. Matrixyl (pal-KTTKS) is used as a topical cosmetic ingredient, not an FDA-approved medicine — cosmetic ingredients are not pre-approved by the FDA the way drugs are, and no Matrixyl drug product exists. It is a "signal peptide" (matrikine) applied to skin in serums/creams (not injected). WADA: not named on the 2026 or 2027 Prohibited List. Legal cosmetic use is not approval as a medicine, and WADA says a peptide that is not named may still be prohibited under S0 (Non-Approved Substances); athletes should check with their anti-doping organization before use. Not DEA-scheduled.

Safety

Matrixyl (pal-KTTKS) is applied topically and was well tolerated in its clinical study. As with any topical, irritation or allergy is possible, so patch-testing a new product is sensible. It is a cosmetic ingredient, not a treatment for any medical skin condition, and it is not injected. It isn't named on the WADA Prohibited List, but WADA says a peptide that isn't named may still be banned, so athletes should check with their anti-doping organization before using it. VialWise is a research and educational reference, not medical advice.

Disclosures

⚠️ Matrixyl (pal-KTTKS) is a topical cosmetic ingredient, not an FDA-approved drug. It is not a treatment for any medical skin condition. Information here is informational, not medical advice.

⚠️ This is a topical, not an injectable. Matrixyl is formulated into serums/creams and applied to the skin — it is not reconstituted for injection like the research peptides elsewhere in this library. The reconstitution guidance below is for dissolving the powder into a topical formulation, not for injecting it.

⚠️ "Matrixyl" covers several products. This entry is pal-KTTKS (palmitoyl pentapeptide-4/-3). Branded blends like Matrixyl 3000 (pal-GHK + pal-GQPR) and Matrixyl Synthe'6 are different formulations with their own (separate) evidence — don't assume the data here applies to those.

Quick reference

Compound classPalmitoyl pentapeptide (pal-KTTKS): the collagen-I fragment KTTKS with a palmitic-acid tail. A "signal peptide" / matrikine in the cosmeceutical classification.[¹][³]
Common vial sizesCosmetic/research-supply lyophilized vials; also sold as pre-diluted cosmetic solutions.
Typical use concentrationThe clinical study used 3 ppm (0.0003%) pal-KTTKS in a moisturizer;[¹] finished cosmetic products commonly use low parts-per-million to fractions of a percent. Formulation figures, not a medical dose.
RouteTopical (serum/cream). Not an injectable.
FrequencyAs part of a daily topical routine, per the finished product.
Onset of actionImprovements in the clinical study were assessed over 12 weeks;[¹] topical anti-aging effects are gradual.
StorageLyophilized powder refrigerated, away from light; formulated solution refrigerated and preserved.

In depth

Matrixyl is the trade name (originally from Sederma) for pal-KTTKS — the pentapeptide KTTKS (lysine-threonine-threonine-lysine-serine, a fragment of the type-I procollagen molecule) with a palmitic-acid ("palmitoyl") tail attached. In the cosmeceutical-peptide classification it is the archetypal "signal peptide" (also called a matrikine): the KTTKS sequence mimics a piece of broken-down collagen, and the presence of such fragments is thought to signal skin fibroblasts to produce new extracellular-matrix components (collagen, etc.), as part of the skin's natural repair signaling.[¹][³]

Why the palmitoyl tail. KTTKS on its own is water-loving and doesn't cross the skin's oily outer barrier well. Attaching the fatty palmitoyl tail makes the molecule able to penetrate. According to PubMed, a skin-permeation study showed exactly this: pal-KTTKS was detected in all skin layers (stratum corneum, epidermis, dermis) while unmodified KTTKS was not detected in any layer, and pal-KTTKS was also more stable against skin enzymes.[²] So the palmitoylation is functionally essential, not cosmetic branding.

Clinical evidence. Matrixyl has one of the stronger evidence bases among cosmetic peptides. In a 12-week, double-blind, placebo-controlled, split-face, randomized clinical study of 93 women (aged 35–55), a moisturizer containing 3 ppm pal-KTTKS was compared against the identical moisturizer without it. The pal-KTTKS product produced significant improvement in fine lines/wrinkles by both quantitative image analysis and expert grading, was well tolerated, and subjects also self-reported fine-line improvement.[¹] Dermatology reviews classify pal-KTTKS as a leading signal-peptide cosmeceutical.[³]

Evidence quality. This is cosmetic-grade clinical evidence — a single well-designed split-face trial plus supportive mechanistic/permeation work — not drug-level proof across many large trials. The split-face design (each subject serves as her own control) is a genuine strength, but effects are modest and the outcome is cosmetic appearance, not a medical endpoint.

Regulatory status (US). Matrixyl is not a drug — it is used as a topical cosmetic ingredient. Cosmetic ingredients are not pre-approved by the FDA the way drugs are. Not DEA-scheduled.

Regulatory status (sport — WADA). Matrixyl is not named on the WADA 2026 or 2027 Prohibited List.[⁴][⁵] Being legal as a cosmetic ingredient is not approval "by any governmental regulatory health authority for human therapeutic use", which is what WADA's S0 (Non-Approved Substances) turns on. In its notes on the 2027 List, WADA says many peptides not approved for human use fall under S0 and that a peptide may still be prohibited even if it is not named.[⁶] The List does not settle how S0 applies to a topical cosmetic, so athletes in drug-tested sport should confirm with their anti-doping organization before use.

Common cosmetic interests. Anti-aging facial serums and creams (fine lines, skin texture) — its established cosmetic use. It is often paired with other actives in finished skincare products.

Reported side effects

Commonly reported

  • Local irritation, redness, or itching at the application site
  • Contact allergy in sensitive individuals
  • No systemic concern is expected from normal topical use.
  • Do not inject this — it is a topical ingredient.

Contraindications and warnings

Not a medical skin treatment — Matrixyl is a cosmetic ingredient; medical skin conditions warrant a clinician and evidence-based options (e.g., topical retinoids where appropriate).

Known allergy/sensitivity to the peptide or formulation — avoid

Broken or compromised skin — avoid applying cosmetic peptides to open or irritated skin

Pregnancy and lactation — topical cosmetic use is generally considered low-risk, but consult a clinician if unsure

Do not inject — this is a topical ingredient with no injection safety data

Regulatory note (US): Cosmetic ingredient, not an FDA-approved drug. Not DEA-scheduled.

Regulatory note (sport): Not named on the WADA 2026 or 2027 Prohibited List[⁴][⁵]; confirm with your anti-doping organization before use (see About).

Key terms

Signal peptide / matrikine
A peptide that mimics a fragment of broken-down skin protein (like collagen) and is thought to 'signal' skin cells to build new matrix. Matrixyl is the classic example.
KTTKS
The five-amino-acid collagen fragment (lysine-threonine-threonine- lysine-serine) at the core of Matrixyl.
Palmitoyl
A fatty acid tail attached to the peptide to help it cross the skin's outer barrier. Without it, KTTKS doesn't penetrate well.
ppm (parts per million)
A very low concentration unit. The Matrixyl trial used 3 ppm — a tiny amount — in a moisturizer.
Topical
Applied to the skin surface (a serum or cream), not swallowed or injected.

Sources

  1. Robinson LR, Fitzgerald NC, Doughty DG, Dawes NC, Berge CA, Bissett DL. (2005). Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. International Journal of Cosmetic Science, 27(3):155–160.(PMID 18492182)
  2. Choi YL, Park EJ, Kim E, Na DH, Shin YH. (2014). Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS). Biomolecules & Therapeutics (Seoul), 22(4):321–327.(PMID 25143811)
  3. Lupo MP, Cole AL. (2007). Cosmeceutical peptides. Dermatologic Therapy, 20(5):343–349.(PMID 18045359)
  4. World Anti-Doping Agency. The 2026 Prohibited List, International Standard (effective 1 January 2026). PDF: wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf. Matrixyl is not named on the 2026 List. Its S0 (Non-Approved Substances) category turns on approval "with no current approval by any governmental regulatory health authority for human therapeutic use".
  5. World Anti-Doping Agency. World Anti-Doping Code International Standard Prohibited List 2027 (effective 1 January 2027). PDF: wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf. Matrixyl is not named. S0 (Non-Approved Substances) keeps its 2026 wording and adds "peptides" to its examples.
  6. World Anti-Doping Agency. Summary of Major Modifications and Explanatory Notes 2027 Prohibited List. PDF: wada-ama.org/sites/default/files/2026-09/2027_list_explanatory_note_en_final_17_august_2026_1.pdf. On S0 (Non-Approved Substances): "Many peptides, not approved for human use by regulatory authorities, fulfill the criteria of the World Anti-Doping Code for inclusion on the Prohibited List and fall under the S0 (Non-Approved Substances) class, or other classes (such as S2 or S4). Even if a peptide is not specifically named on the List, utmost caution should be taken as it may still be prohibited and may be harmful to health."

Related entries

Entry last updated 2026-09-03. Sourced from published literature and regulatory labelling; see Sources above.