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AMIRAVOResearch Library
Skin

Matrixyl

Also known as Palmitoyl pentapeptide-4 · Palmitoyl pentapeptide-3 · Pal-KTTKS · C16-KTTKS · Palmitoyl-Lys-Thr-Thr-Lys-Ser · Lipopentapeptide 3

Not approved — research use onlyBLimited human dataWhat this means

Matrixyl is the trade name of palmitoyl pentapeptide-4 (pal-KTTKS), a cosmetic ingredient based on a fragment of type I procollagen with a palmitic acid tail; the main human study is a 12-week industry split-face trial in 93 women reporting reduced fine lines versus the same moisturizer without it, with cell work suggesting collagen stimulation and skin studies showing poor permeation.

US status
Not approved — research use only
Evidence
Grade B
Half-life
Not located in the sources reviewed. In skin extracts and homogenates both the unmodified pentapeptide and the palmitoylated form were rapidly degraded, with the palmitoylated form more stable; protease inhibitors improved the stability of both (mouse skin preparations) 4.
Class
Palmitoylated synthetic pentapeptide (peptide amphiphile); cosmetic ingredient derived from a type I procollagen fragment
Studied in: Skin research
More
Log a sample
Dosing referenceCycle-length evidence
Unbranded reference vial illustrating Matrixyl; not an actual product
Research reference, not advice. No administration data. Amiravo sells nothing; some links are referrals.Read the full notice

Key takeaways

  • Matrixyl is palmitoyl pentapeptide-4 (pal-KTTKS), a cosmetic ingredient based on a type I procollagen fragment with a palmitic acid tail, not an approved drug 7,9.
  • The main human evidence is a single 12-week double-blind, split-face randomized study in 93 women, conducted by the ingredient's manufacturer, which reported reduced wrinkles and fine lines versus the same moisturizer without the peptide 1.
  • Cell work supports a collagen-stimulating action: in human fibroblasts the palmitoylated peptide increased collagen production in a concentration-dependent way tied to its self-assembly into nanotapes 2.
  • Skin-permeation work is less encouraging: in excised mouse skin the palmitoylated peptide reached the stratum corneum, epidermis and dermis but did not permeate into the receptor compartment, and both forms degraded rapidly in skin preparations 4.
  • No FDA approval exists and it is not named individually in the WADA sources reviewed; S0 covers substances without governmental approval for human therapeutic use 9,10.

Development stage

Where Matrixyl sits between laboratory work and regulatory approval.

  1. Preclinical (current)
  2. Phase 1
  3. Phase 2
  4. Phase 3
  5. Approved

Stage comes from the regulatory record and ClinicalTrials.gov studies naming the compound (for compounds approved nowhere, only completed trials or trials with posted results count) (checked 2026-10-24). A registered trial is not a result.

Mechanism of action

Palmitoyl pentapeptide-4 joins the pentapeptide Lys-Thr-Thr-Lys-Ser, a sequence corresponding to a fragment of the type I procollagen propeptide, to palmitic acid at the N-terminus 2,7. The stated rationale is that such collagen fragments act as feedback signals to dermal fibroblasts, so that applying the fragment stimulates new extracellular matrix production; the palmitoyl tail is added to improve passage into the lipophilic stratum corneum 1,2.

Evidence for the mechanism

  • Fibroblast response: in human dermal and corneal fibroblasts, collagen production rose in a concentration-dependent manner close to the peptide's critical aggregation concentration, which the authors interpreted as linking self-assembly into nanotape structures to the collagen effect 2.
  • Wound models: in rats, the peptide was associated with greater collagen density, angiogenesis and epitheliogenesis than untreated wounds 5, and a separate rat study related its effect to connective tissue growth factor and alpha-smooth muscle actin expression during wound contraction 8.

Delivery

In excised hairless mouse skin, neither the unmodified pentapeptide nor the palmitoylated form was detected in the receptor solution; the palmitoylated form was recovered from the stratum corneum, epidermis and dermis, while the unmodified peptide was undetectable in any layer, indicating the palmitoyl tail helps the peptide enter but not cross skin 4. Microneedle treatment of excised human skin increased signal for pal-KTTKS by several fold, and liposome encapsulation has been characterised as another delivery strategy 6,11.

Molecular structure

PubChem CID 9897237 ↗
2D chemical structure of Matrixyl

2D depiction generated from the PubChem record. Depictions are schematic and do not show salt form, counter-ions or conformation.

Formula
C39H75N7O10
Molecular weight
802.1 g/mol
CAS
214047-00-4
InChIKey
WSGCRSMLXFHGRM-DEVHWETNSA-N

Research overview

Human research

The principal study is a 12-week, double-blind, placebo-controlled, split-face, left-right randomized comparison in 93 white women aged 35 to 55 of a moisturizer containing the peptide against the same moisturizer alone, carried out at Procter and Gamble laboratories; the authors reported significant improvement versus the control product for wrinkles and fine lines by quantitative technical and expert-grader image analysis, with participants also reporting fine-line change in self-assessment and no skin tolerability problems 1. In a later double-blind randomized trial, 21 Indonesian women aged 26 to 55 with crow's feet used palmitoyl pentapeptide-4 cream, acetyl hexapeptide-3 cream or placebo for eight weeks with corneometry, tewametry, cutometry, photography and a grading scale; the authors judged the palmitoyl pentapeptide-4 arm to show more change than the other two arms and described the study as an initial one requiring a larger sample and longer duration 3. Excised human skin has been used for permeation work rather than clinical outcomes 6.

Animal research

In a rat wound-healing comparison of patches and creams containing the peptide against a vehicle patch, a vehicle cream, a commercial dressing and an untreated control over 21 days, treated groups showed greater wound-area reduction (from 63.5% up to 81.8% versus the untreated control) with greater collagen density, angiogenesis and epitheliogenesis, and re-epithelialization greater for the patch than for the cream 5. A separate rat study examined the peptide's effect on wound contraction in relation to connective tissue growth factor and alpha-smooth muscle actin expression 8. In excised hairless mouse skin, the palmitoylated peptide was more stable than the unmodified peptide but neither crossed full-thickness skin 4.

In-vitro research

In human dermal and corneal fibroblasts, the peptide amphiphile stimulated collagen production in a concentration-dependent manner near its critical aggregation concentration, which the authors tied to self-assembly into nanotapes 2. Liposome encapsulation of the peptide has been structurally and functionally characterised as a delivery approach 11. In excised human skin, microneedle pretreatment increased the delivered signal for pal-KTTKS by a factor of 2 to 22 relative to passive application 6.

Key studies

  1. Robinson et al., Int J Cosmet Sci (2005)
    12-week double-blind, placebo-controlled, split-face, left-right randomized study of a moisturizer with the peptide versus the same moisturizer; conducted by the ingredient's manufacturer
    Model: Humans (93 white women aged 35 to 55)

    Reported significant improvement versus the control product in wrinkles and fine lines by quantitative image analysis and expert grading, with participant-reported fine-line change and no skin tolerability problems.

  2. Jones et al., Mol Pharm (2013)
    Cell culture with pyrene fluorescence determination of critical aggregation concentration
    Model: Cells (human dermal and corneal fibroblasts)

    Collagen production rose in a concentration-dependent manner close to the critical aggregation concentration, suggesting self-assembly and collagen stimulation are inter-related.

  3. Aruan et al., J Clin Aesthet Dermatol (2023)
    Double-blind randomized three-arm trial over eight weeks with instrumental and photographic assessment
    Model: Humans (21 Indonesian women aged 26 to 55 with crow's feet)

    The authors judged the palmitoyl pentapeptide-4 arm to show more change than the acetyl hexapeptide-3 arm and placebo, and described the study as preliminary with an inadequate sample size.

  4. Choi et al., Biomol Ther (Seoul) (2014)
    LC-MS/MS stability and Franz-cell permeation study
    Model: Ex vivo (hairless mouse skin extracts, homogenates and full-thickness skin)

    Both peptides degraded rapidly, the palmitoylated form more stable; neither reached the receptor solution, and only the palmitoylated form was detected in stratum corneum, epidermis and dermis.

  5. Kachooeian et al., ACS Omega (2022)
    Seven-group controlled animal study over 21 days comparing patch and cream delivery with vehicle, commercial dressing and untreated controls
    Model: Animals (rat wound model)

    Wound-area reduction was greater in peptide-treated groups than in untreated controls, with greater collagen density and re-epithelialization favouring the patch.

  6. Mohammed et al., PLoS One (2014)
    Franz-cell penetration study with confocal imaging of fluorescently tagged peptides, with and without microneedles
    Model: Ex vivo (excised full-thickness human skin)

    Microneedle pretreatment increased delivered signal for pal-KTTKS and two other cosmetic peptides by 2- to 22-fold relative to passive application.

Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

Emerging safety signals

  • In the 12-week manufacturer-run split-face study in 93 women, the authors reported no skin tolerability problems; the study was not sized to detect uncommon events and was conducted at a cosmetic formulation concentration 1. 1 (2005)
  • No independent human safety assessment of palmitoyl pentapeptide-4 was located in the sources reviewed, and the ingredient does not appear in any category of FDA's 503A bulk drug substances list 9. 9 (2026)

What is not known: The size and durability of any cosmetic effect are uncertain: the one substantial human study was conducted by the ingredient's manufacturer and has not been replicated independently at that scale, and the later independent trial had 21 participants and was described by its authors as preliminary 1,3. Whether enough peptide reaches the dermis from an ordinary topical vehicle is unresolved, since in excised skin it entered the skin layers but did not cross, and both peptide forms degrade rapidly in skin preparations 4,6. No human pharmacokinetic or half-life data were identified. No independent published safety assessment, no long-term use data and no comparison against established dermatologic treatments were located 9.

Background viewing

We haven't found a clinician video focused on Matrixyl yet. Meanwhile, this widely watched talk covers the science of aging in general. It does not discuss Matrixyl.

David Sinclair, PhD (Harvard Medical School) on the biology of aging
The Diary Of A CEO · 6.9M views · 2026

These creators are not affiliated with Amiravo and do not endorse Amiravo or any product linked on this site. Nothing here is medical advice. Video views counted on YouTube as of Oct 24, 2026.

Regulatory status

Status
A cosmetic ingredient, not an approved drug. Cosmetic ingredients in the United States are not subject to FDA premarket approval, and palmitoyl pentapeptide does not appear in any of the three categories of FDA's 503A bulk drug substances list as updated May 14, 2026 9. The principal human study was conducted by the ingredient's manufacturer 1.
United States (FDA)
Marketed as a cosmetic ingredient rather than a drug. Cosmetic ingredients in the United States are not subject to FDA premarket approval, and palmitoyl pentapeptide does not appear in any of the three categories of FDA's 503A bulk drug substances list as updated May 14, 2026 9. Absence from drug databases is therefore expected and says nothing about efficacy.
Sport (WADA)
Not named individually in the sources reviewed; S0 covers substances without governmental approval for human therapeutic use, prohibited at all times 10. Cosmetic status does not by itself place a substance outside the List, so athletes should seek a ruling from their anti-doping organisation.

Status varies by country and changes over time. How we describe regulatory status.

Quality and testing notes

A certificate of analysis should state the exact sequence, confirm palmitoylation and say which residue carries the palmitoyl group, since the unmodified pentapeptide behaves differently in skin [4]. Expect identity by mass spectrometry against the calculated mass for C39H75N7O10 (average mass about 802 Da), purity by reverse-phase HPLC with the trace and integration shown, net peptide content separate from gross weight, counter-ion identity (acetate or trifluoroacetate; PubChem also lists a Matrixyl acetate form) and water content [7]. Because the molecule is a peptide amphiphile that self-assembles above a critical aggregation concentration, solution behaviour is concentration-dependent and physical appearance alone is not a purity indicator [2]. For a cosmetic raw material, microbial limits and heavy-metal testing are conventional.

How purity testing works · Reading a certificate of analysis

Check a Matrixyl certificate of analysis against its expected mass (802.1 Da)

Storage and handling

General research-context handling only. Lyophilised lipopeptides of this type are generally kept dry, cool and protected from light and moisture; aqueous preparations are treated as short-lived, and the peptide is rapidly degraded by proteases in skin preparations [4]. Finished cosmetic formulations follow the manufacturer's own stability data. Defer to supplier documentation for the specific lot.

Frequently asked questions

What is Matrixyl?
It is the trade name for palmitoyl pentapeptide-4, or pal-KTTKS: the pentapeptide Lys-Thr-Thr-Lys-Ser from a type I procollagen fragment, with palmitic acid attached 2,7.
What human evidence exists?
Mainly one 12-week double-blind split-face randomized study in 93 women, run by the ingredient's manufacturer, which reported reduced wrinkles and fine lines versus the same moisturizer without the peptide 1. A later independent trial in 21 women reported change over eight weeks but was described by its authors as preliminary 3.
How is it supposed to work?
Collagen fragments are proposed to act as feedback signals to dermal fibroblasts. In human fibroblasts the palmitoylated peptide increased collagen production in a concentration-dependent way tied to its self-assembly 2.
Does it get into the skin?
Partly. In excised mouse skin the palmitoylated form was recovered from the stratum corneum, epidermis and dermis but did not cross into the receptor compartment, while the unmodified peptide was undetectable in any layer 4. Microneedling increased delivery in excised human skin 6.
How does it compare with Argireline in a head-to-head study?
In the only direct comparison located, a three-arm trial in 21 women with crow's feet, the authors judged the palmitoyl pentapeptide-4 arm to show more change than the acetyl hexapeptide-3 arm and placebo over eight weeks; the sample was small and the authors called for larger study 3.
What does the animal work show?
In rat wound models, the peptide was associated with greater wound-area reduction, collagen density and re-epithelialization than untreated controls, with patch delivery outperforming cream 5,8.
Is it FDA-approved?
No. It is a cosmetic ingredient; cosmetic ingredients do not undergo FDA premarket approval in the United States, and it does not appear in any category of FDA's 503A bulk drug substances list 9.
Is it banned in sport?
It is not named individually in the sources reviewed. S0 covers any pharmacological substance with no current governmental approval for human therapeutic use, prohibited at all times, so athletes should ask their anti-doping organisation 10.

Latest indexed research

No new studies were filed in the last sweep.

Search all studies on Matrixyl (PubMed, Europe PMC, ClinicalTrials.gov)

Listed by publication type from the index record. Inclusion is not an endorsement; open the source to read the findings.

Revision history

Meaningful changes to this entry, with dates and sources. Last reviewed Oct 24, 2026. Typo and layout fixes are not listed.

  • New section· entryOct 24, 2026

    New research reference added: Matrixyl.

References

  1. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin Int J Cosmet Sci. 2005
  2. Collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts Mol Pharm. 2013
  3. Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet J Clin Aesthet Dermatol. 2023
  4. Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS) Biomol Ther (Seoul). 2014
  5. Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing ACS Omega. 2022
  6. Microneedle enhanced delivery of cosmeceutically relevant peptides in human skin PLoS One. 2014
  7. Palmitoyl Pentapeptide-4 (CID 9897237) PubChem. 2026
  8. Effect of Palmitoyl-Pentapeptide (Pal-KTTKS) on Wound Contractile Process in Relation with Connective Tissue Growth Factor and alpha-Smooth Muscle Actin Expression Tissue Eng Regen Med. 2017
  9. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (updated May 14, 2026); no entry for palmitoyl pentapeptide or matrixyl in any of the three categories FDA. 2026
  10. International Standard: Prohibited List 2026 World Anti-Doping Agency. 2026
  11. Liposome Encapsulation of the Palmitoyl-KTTKS Peptide: Structural and Functional Characterization Pharmaceutics. 2024

Last reviewed October 24, 2026 by the Amiravo editorial team.

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Laboratory arithmetic with every formula shown.

For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page is educational and is not medical advice.

Unbranded reference vial illustrating Matrixyl; not an actual product

Unbranded reference image. Amiravo does not produce, supply or sell this compound.

Specifications

Molecular formula
C39H75N7O10
Molecular weight
802.1 g/mol
CAS number
214047-00-4
PubChem CID
9897237
ChEMBL
CHEMBL451881
Sequence
Palmitoyl-Lys-Thr-Thr-Lys-Ser (pal-KTTKS)
Type
Single compound

Identifiers from PubChem. Verify against the supplier’s documentation for your lot.

Research stats

How much has been published, not how good it is.

PubMed records
33
Indexed as human research
18
Animal-only research
2
Randomized controlled trials
2
Registered trials
0
Trials with posted results
0
FDA adverse-event reports (FAERS)
1
2006: 02007: 02008: 02009: 32010: 02011: 02012: 12013: 22014: 22015: 02016: 02017: 22018: 12019: 62020: 12021: 22022: 22023: 12024: 42025: 32026: 420062026
PubMed records per year (current year is partial).

Counts from title/abstract searches of PubMed, ClinicalTrials.gov, openFDA and NIH RePORTER, checked 2026-10-24. Names shared with other substances can inflate counts. FAERS reports are spontaneous and do not establish cause. Funding shows interest, not evidence. Method

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