Matrixyl

Technical data

INN name

Palmitoyl Pentapeptide-4

CAS

214047-00-4

Molecular formula

C39H75N7O10

Molecular weight

802.06 g/mol

Identity and composition

Matrixyl (palmitoyl pentapeptide-4, or Pal-KTTKS) is a matrikine for cosmetic/dermatological use that is studied for its role as a signal in the production of the skin's extracellular matrix. It is the pentapeptide KTTKS linked to palmitic acid, used in in vitro topical research.

Reference chemical identity data:

• Name / synonyms: Palmitoyl Pentapeptide-4, Pal-KTTKS, N-palmitoyl-KTTKS, Matrixyl
• CAS: 214047-00-4
• Molecular formula: C39H75N7O10
• Molecular weight: 802.1 g/mol
• Sequence: Pal-Lys-Thr-Thr-Lys-Ser (pentapeptide KTTKS with a palmitoyl group at the N-terminal end)

In the literature there is some nomenclature ambiguity between "pentapeptide-3" and "pentapeptide-4" when referring to the same compound.

Product for research use.

Mechanism of action

Matrixyl is the pentapeptide KTTKS (Lys-Thr-Thr-Lys-Ser) conjugated with palmitic acid at the N-terminal end. KTTKS is a matrikine: it corresponds to a fragment derived from the proteolytic hydrolysis of type I collagen (a subsequence of the alpha-1 chain of procollagen I) that acts as a feedback signal. In in vitro studies it has been observed to stimulate extracellular matrix production and the expression of type I and III collagen in fibroblasts (PMID 31618846).

Palmitoylation does not alter the active peptide sequence; it is added to confer lipophilic character, increase resistance to proteases, and improve penetration through the stratum corneum. In skin studies, Pal-KTTKS was retained in the stratum corneum, epidermis, and dermis, whereas free KTTKS was not detected in any layer, which motivates the lipid conjugation (PMID 31618846).

In wound and fibroblast models, Pal-KTTKS showed effects dose-dependent on markers such as CTGF and the expression of alpha-SMA, as well as on the contraction of collagen lattices (PMID 30603464).

Pharmacokinetics

No such was located systemic half-life (t½) documented in the reviewed sources. The available data are of a dermal/topical type: in skin studies, Pal-KTTKS is retained in the cutaneous layers (stratum corneum, epidermis and dermis), whereas unmodified KTTKS is not detected, which indicates that palmitoylation improves cutaneous retention and stability (PMID 31618846).

No quantitative data on systemic absorption, metabolism, or elimination are available.

Scientific evidence

The available evidence is mostly preclinical and laboratory-based, and must be interpreted with caution. Matrixyl is a cosmetic/dermatological ingredient (a matrikine), not a drug in conventional clinical development; no records were identified on ClinicalTrials.gov with a formal phase for this compound as a single agent.

Most of the data come from in vitro models (fibroblast cultures, collagen contraction assays, cutaneous penetration) and from some cosmetic studies of topical application (PMID 31618846; PMID 30603464). Claims about collagen synthesis and anti-aging effects should be interpreted with reservations, since they do not come from controlled phased clinical trials. The magnitude of any increase in collagen synthesis in humans is not confirmed in controlled trials.

Research applications

Product for research use.

Aimed at research lines such as:

• In vitro fibroblast studies on the expression of extracellular matrix and type I and III collagen.
• Skin penetration and retention assays comparing the palmitoylated peptide against the free matrikine.
• Collagen contraction models and fibroblast-associated markers (CTGF, alpha-SMA).

Not applicable for:

• clinical use, food use, or therapeutic administration in humans or animals.
• Clinical or diagnostic use: it is not an approved drug and there is no evidence from controlled phase trials supporting clinical uses.

Research protocols

The described doses correspond to concentrations used in laboratory studies, not to guidelines for human use, and are presented only as a research reference.

In a wound model, a dose window: low concentrations (~0.1 µM) were associated with less trans-differentiation of fibroblasts to myofibroblasts and less contraction, while higher concentrations (~0.5 µM) attenuated that effect, which suggests a dose dependence (PMID 30603464).

No standardized dosing protocols for use in humans, nor validated clinical guidelines, were found. Any working concentration must be defined by the researcher according to their experimental design.

Reconstitution

General laboratory handling guide (not a guideline for use in humans):

• For lyophilized peptides it is customary to reconstitute with bacteriostatic water (water with ~0.9% benzyl alcohol), which helps limit microbial growth in vials for repeated use.
• It is recommended to add the solvent slowly down the wall of the vial, letting it run over the powder, without directing the stream directly at the pellet.
• Swirl the vial gently until complete dissolution; avoid vigorous agitation or vortexing, which can stress the peptide.
• Calculate the reconstitution volume according to the working concentration desired for the experiment.

Stability and storage

Laboratory handling standard for peptides:

• Lyophilized: in powder form it usually remains stable when stored cold; for prolonged preservation, freezing is preferred, protected from moisture and light.
• Reconstituted: in solution stability is lower; it is advisable to keep it refrigerated and use it within a short window of time, avoiding repeated freeze-thaw cycles.
• One advantage described for Pal-KTTKS over free KTTKS is its greater resistance to proteases and better skin retention, attributed to palmitoylation (PMID 31618846).

Always consult the specific conditions of the lot and the supplier.

Safety profile

The documented safety profile corresponds to the topical cosmetic use and laboratory models, not to systemic administration in humans.

• In the reviewed studies, the palmitoylated forms of KTTKS were non-cytotoxic for fibroblasts at the concentrations tested (PMID 31618846).
• In a wound model, a dose dependence: low doses reduced trans-differentiation into myofibroblasts and contraction, whereas higher concentrations attenuated that effect (PMID 30603464).
• No systemic toxicity data in humans were found.

Because it is a research product, it must be handled with the usual laboratory precautions and not administered to humans or animals.

Comparative context

Compared to the free KTTKS (the unmodified matrikine), Pal-KTTKS is more stable against proteases and penetrates and is retained better in the skin, which is why it is preferred for topical-application work (PMID 31618846).

Matrixyl belongs to the class of matrikines / cosmetic signaling peptides, which act by stimulating extracellular-matrix signals. This class is distinct from other groups of peptides with different mechanisms, for example:

• Copper-carrier peptides (such as GHK-Cu), which transport copper and act by another pathway.
• Neuromuscular-acting peptides (such as Argireline / acetyl hexapeptide-8), focused on neuromuscular signaling.

In addition, it has been described that a series of palmitoylated analogs of KTTKS showed greater protease inhibition while remaining non-cytotoxic to fibroblasts (PMID 31618846).

History and development

Matrixyl is a cosmetic/dermatological ingredient of the matrikine class, introduced commercially by Sederma. It was developed from the pentapeptide KTTKS, a fragment derived from the hydrolysis of type I collagen, to which a palmitoyl group was added at the N-terminus to improve its stability against proteases and its cutaneous penetration.

No records were identified on ClinicalTrials.gov with a formal phase for this compound as a single agent; its trajectory corresponds to that of a cosmetic ingredient studied mainly in in vitro models and in topically applied cosmetic studies (PMID 31618846; PMID 30603464).

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Scientific references (6)

Peer-reviewed literature on Matrixyl, with its PubMed identifier when available:

• Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing (Kachooeian M et al. · ACS Omega · 2022) PMID 35874243.
• Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin (Robinson, et al. · International Journal of Cosmetic Science · 2005) PMID 18492182.
• Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS) (Choi, et al. · Biomolecules & Therapeutics · 2014) PMID 25143811.
• Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet. (Aruan RR, et al. · J Clin Aesthet Dermatol · 2023) PMID 36909866.
• Collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts. (Jones RR, et al. · Mol Pharm · 2013) PMID 23320752.
• Effect of Palmitoyl-Pentapeptide (Pal-KTTKS) on Wound Contractile Process in Relation with Connective Tissue Growth Factor and α-Smooth Muscle Actin Expression. (Park H, et al. · Tissue Eng Regen Med · 2017) PMID 30603464.

Guides and articles about Matrixyl

Lecturas del blog de EXOMA que la editorial asoció a este compuesto:

• Peptides for the Skin: Anti-Wrinkle, Collagen and Regeneration [2026 Guide]

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