--- title: "Palmitoyl Pentapeptide-4: Research & Evidence" url: https://www.bodyhackguide.co/compound/palmitoyl-pentapeptide-4 description: "Palmitoyl Pentapeptide-4: mechanism, clinical studies & side effects." lang: en --- Skip to content Compare notes on r/BodyHackGuide (https://reddit.com/r/bodyhackguide) Compare notes with other researchers. Join r/BodyHackGuide (https://reddit.com/r/bodyhackguide) Image: Palmitoyl Pentapeptide-4 molecular structure (https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/9897237/PNG?image_size=300x300) # Palmitoyl Pentapeptide-4 Skin & Hair (https://www.bodyhackguide.co/wiki#cat-skin-&-hair)Marketed topical cosmetic ingredient with a small set of human cosmetic trials Also known as: Pal-KTTKS, Matrixyl, Palmitoyl pentapeptide-3, Pal-Lys-Thr-Thr-Lys-Ser, Lipopentapeptide 3, N2-(1-oxohexadecyl)-L-lysyl-L-threonyl-L-threonyl-L-lysyl-L-serine Palmitoyl pentapeptide-4 is the cosmetic ingredient Pal-KTTKS, a five-amino-acid fragment of the type I collagen propeptide with a 16-carbon palmitic acid chain attached, sold to formulators under the trade name Matrixyl (PubChem CID 9897237; PMID: 8486721). The peptide half, Lys-Thr-Thr-Lys-Ser, was identified in 1993 by Katayama and colleagues at the University of Tennessee as the shortest piece of the collagen propeptide that still stimulated production of collagen I, collagen III and fibronectin in cultured cells, and the palmitoylated version is sold as a Sederma cosmetic ingredient (PMID: 8486721; PMID: 18503476). Price check No vendor listings yet We do not track a vendor for Palmitoyl Pentapeptide-4 yet. Compare other compounds: https://www.bodyhackguide.co/compare Half-life: No published human value Route: Topical MW: 802.1 g/mol CAS: 214047-00-4 (PubChem CID 9897237 Last reviewed: Oct 21, 2026 ## Overview ### At A Glance Mechanism Where the sequence comes from… Half-Life No published human value. The relevant measurements are stability in skin rather than plasma. In hairless mouse skin extracts and homogenates both KTTKS and pal-KTTKS were degraded rapidly, with pal-KTTKS the more stable of the two, and adding protease inhibitors improved the stability of both (PMID: 25143811). In rat skin homogenate the free peptide was described as very susceptible to peptide bond cleavage by aminopeptidases present in the skin (PMID: 22921149). Routes Topical Potential Benefits Reduction in wrinkles and fine lines against a placebo moisturizer by image analysis and expert grading in 93 women over 12 weeks at 3 parts per million (PMID: 18492182) Improvement in several subjects by clinical photographs and data over 8 weeks in 21 Indonesian women, where the authors judged palmitoyl pentapeptide-4 better than acetyl hexapeptide-3 cream and placebo (PMID: 36909866) Concentration-dependent collagen production in cultured human dermal and corneal fibroblasts (PMID: 23320752) Stimulation of collagen I, collagen III and fibronectin production in mesenchymal cells, the finding that defined the sequence (PMID: 8486721) Reduced conversion of human fibroblasts into alpha-smooth muscle actin positive myofibroblasts at 0.1 micromolar in culture (PMID: 30603464) Faster wound area reduction and higher collagen content than untreated controls in 42 Wistar rats over 21 days, as a cream or a loaded patch (PMID: 35874243) Lower periorbital skin roughness after 4 weeks in two split-face studies of multi-ingredient products that contained it alongside niacinamide, Pal-KT and carnosine (PMID: 19735523) Safety Notes Common Described as well tolerated by the skin at 3 parts per million over 12 weeks in 93 women (PMID: 18492182) No adverse event is reported either way in the 21-subject 8-week periorbital trial (PMID: 36909866) No adverse event is reported either way in two split-face studies of multi-ingredient products containing it (PMID: 19735523) Serious In the one trial that recorded adverse events, a three-active cream containing Matrixyl on irradiated skin produced one suspected allergic reaction and more frequent itching, with no benefit over dexpanthenol lotion (PMID: 15127162) No repeat-dose human safety study, no pregnancy data, and no data on any route other than topical were found Dose direction matters in culture: 0.1 micromolar reduced myofibroblast conversion while 0.5 micromolar did not, and the authors flagged the repair versus fibrosis balance (PMID: 30603464) ### Mechanism of Action ### Where the sequence comes from Fibril-forming collagens are made as precursors whose end pieces are cut off outside the cell, and those freed fragments appear to feed back on collagen synthesis. Katayama's group had shown that a subfragment of the carboxyl-terminal propeptide of type I collagen, residues 197 to 241, strongly increased extracellular matrix production in cultured fibroblasts, and in 1993 they dissected that fragment down to the pentapeptide Lys-Thr-Thr-Lys-Ser, residues 212 to 216, as the minimum sequence that still produced potent stimulation of collagen and fibronectin production across several mesenchymal cell types (PMID: 8486721). PubChem labels the unmodified peptide accordingly, as procollagen type I residues 212 to 216 (PubChem CID 9959565). A peptide released from a matrix protein that then signals back to the cells is called a matrikine, and a 2011 paper setting out that concept names KTTKS as its example (PMID: 21692860). ### What it does to cells The measured effect is matrix synthesis, not muscle relaxation or pigment control. A 2011 review of the published work concluded there is a sound in vitro basis for an effect on fibroblasts, with the stimulation specific to collagen types I and III and to fibronectin (PMID: 21535443). In human dermal and corneal fibroblasts, the palmitoylated form raised collagen production in a concentration-dependent way (PMID: 23320752). Designed variants built on the same motif raise collagen and fibronectin in human adipose-derived stem cells (PMID: 28467727), and an acetylated analogue increased collagen synthesis in fibroblasts by about 80 percent in culture (PMID: 27184584). Conjugates that attach the peptide to lipoic acid or to ascorbic acid stimulate collagen more than either part alone in cell culture (PMID: 24090916; PMID: 19944016). ### Why the palmitate tail is there The peptide alone is small, water-loving and charged, which is poor for crossing the stratum corneum. Karl Lintner at Sederma published the general approach in 2000: long-chain fatty acid conjugates improve skin penetration, specific activity and economic feasibility for peptide actives (PMID: 18503476). Physical chemistry work at the University of Reading, with two Procter and Gamble co-authors, showed the consequence. The palmitoylated peptide self-assembles above a critical aggregation concentration into flat tapes and fibres with high beta-sheet content, which the related palmitoyl peptides Pal-GHK and Pal-KT do not form in the same way (PMID: 23822110), and collagen stimulation in fibroblasts tracked concentration close to that critical aggregation concentration, which the authors read as self-assembly and activity being linked (PMID: 23320752). The chain-length series C14, C16 and C18 was studied on the same assumption, that the lipid chain acts as a prodrug handle and the peptide is released by enzymes in skin (PMID: 22834769). ### How far it actually gets into skin This is the weak point of the whole class, and the published measurements are modest. The 2011 review noted a surprising absence of in vitro skin penetration data at that time (PMID: 21535443). A 2014 Korean study measured both forms in hairless mouse skin: both were rapidly degraded in skin extracts and homogenates, with the palmitoylated form the more stable of the two, and protease inhibitors improved both. Neither compound reached the receptor fluid under the mouse skin. Unmodified KTTKS was not detected in any skin layer, while pal-KTTKS was found at 4.2 plus or minus 0.7 micrograms per square centimetre in the stratum corneum, 2.8 plus or minus 0.5 in the epidermis and 0.3 plus or minus 0.1 in the dermis (PMID: 25143811). A separate method paper showed the free peptide is cleaved quickly by aminopeptidases in rat skin homogenate (PMID: 22921149). In excised human skin, microneedles raised the fluorescence signal from pal-KTTKS and two other cosmetic peptides by 2 to 22 fold over passive application (PMID: 25033398). ### A dose-direction finding worth knowing More is not simply better in the one study that looked for a turning point. In human fibroblast cultures and collagen lattices, pal-KTTKS at 0.1 micromolar halved the proportion of cells carrying alpha-smooth muscle actin stress fibres, from 75 plus or minus 7.1 percent to 38.6 plus or minus 16.1 percent, which the authors read as less conversion of fibroblasts into the myofibroblasts that drive scarring; at 0.5 micromolar the effect was not significant. They concluded that the balance between wound-healing and pro-fibrotic actions has to be considered when choosing a dose (PMID: 30603464). ### Names that get mixed up Three naming traps run through the market copy. First, the INCI name Pentapeptide-4 means the bare peptide KTTKS, while Palmitoyl pentapeptide-4 means the palmitoylated version, and the same palmitoylated molecule was called Palmitoyl pentapeptide-3 under older nomenclature (PubChem CID 9897237; PubChem CID 9959565). Second, the 2011 review points out that KTTKS became loosely associated with the word pentapeptide in cosmetic copy even though many unrelated five-residue peptides exist (PMID: 21535443). Third, Matrixyl and Matrixyl 3000 are not the same thing: the peptides described in the literature as present in Matrixyl 3000 are palmitoyl tripeptide-1 (Pal-GHK) and palmitoyl tetrapeptide-7 (Pal-GQPR), neither of which is Pal-KTTKS (PMID: 42790608). ### Overview Palmitoyl pentapeptide-4 is the cosmetic ingredient Pal-KTTKS, a five-amino-acid fragment of the type I collagen propeptide with a 16-carbon palmitic acid chain attached, sold to formulators under the trade name Matrixyl (PubChem CID 9897237; PMID: 8486721). The peptide half, Lys-Thr-Thr-Lys-Ser, was identified in 1993 by Katayama and colleagues at the University of Tennessee as the shortest piece of the collagen propeptide that still stimulated production of collagen I, collagen III and fibronectin in cultured cells, and the palmitoylated version is sold as a Sederma cosmetic ingredient (PMID: 8486721; PMID: 18503476). The human evidence is a small set of topical cosmetic trials, the largest being a 12-week study in 93 women whose first author is at Procter and Gamble, plus one 21-subject trial in Indonesia that compared it against acetyl hexapeptide-3 (PMID: 18492182; PMID: 36909866). Palmitoyl pentapeptide-4 is not an FDA-approved drug, and no study of it is registered on ClinicalTrials.gov, checked on 20 October 2026. ### Potential Research Fields Cosmetic science Skin aging Collagen biology Topical peptide delivery Wound healing ## Chemical Information IUPAC Name Not yet available CAS Number 214047-00-4 (PubChem CID 9897237; FDA unique ingredient identifier KK181SM5JG). The unmodified peptide KTTKS, INCI name Pentapeptide-4, is a separate substance with CAS 149128-48-3. Molecular Formula C39H75N7O10 Molecular Mass 802.1 g/mol View on PubChem: https://pubchem.ncbi.nlm.nih.gov/compound/9897237 ## Dosing & Protocols ### Unlock the Dosing tab Enter your email to keep reading. It is free, and it opens these tabs on every compound page in this browser. - Route You also get the free peptide cheat sheet by email. Unsubscribe anytime. Have an account? Sign in (https://www.bodyhackguide.co/auth) ## Research ### Unlock the research summary - A summary of the key research - Safety and side effects - A link to the PubMed results ## Interactions ### Interaction Matrix ### Contraindications There is no drug labelling for palmitoyl pentapeptide-4, so there is no contraindication list. The cautions that follow from the published work are narrow. One human trial recorded a suspected allergic reaction and more frequent itching in the arm receiving a three-active cream that contained Matrixyl, in patients whose skin was already being irradiated (PMID: 15127162). Irradiated or broken skin is a setting where a cosmetic peptide cream has been tested once and did not help. The ingredient increases collagen and fibronectin production by design (PMID: 8486721), and the balance between helpful matrix synthesis and myofibroblast conversion shifted with concentration in culture (PMID: 30603464), which is a reason to treat scar-prone skin as an open question rather than an established use. Delivery is formulation-dependent: an analytical study of anti-wrinkle creams found that the formulation influenced how much pal-KTTKS was available in the product (PMID: 19393372), and in mouse skin the peptide reached the dermis only in small amounts (PMID: 25143811). Microneedling raised peptide signal in excised human skin by 2 to 22 fold (PMID: 25033398), so any device that breaks the barrier changes the exposure that the cosmetic trials tested. Nothing has been published on use in pregnancy, on children, or by any route other than topical. Research Disclaimer This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds. No listings found for Palmitoyl Pentapeptide-4. ### Sign in to leave a review Reviews on BodyHackGuide are tied to verified user accounts and moderated before publishing. Sign in (free, no spam) to share your experience with Palmitoyl Pentapeptide-4. ### Related Compounds View All (https://www.bodyhackguide.co/wiki) ### Acetyl Hexapeptide-8 Skin & Hair Marketed topical cosmetic ingredient (INCI: Acetyl Hexapeptide-8 / Argireline). Supported by small human anti-wrinkle studies, including one randomized, placebo-controlled trial; no systemic or injectable clinical development. Not an FDA-approved drug. Acetyl Hexapeptide-8 (INCI: Acetyl Hexapeptide-3 in older nomenclature, commercially known as Argireline) is a synthetic hexapeptide designed as a competitive inhibitor of the SNARE complex at the neuromuscular junction. t½ Short (topical application, no systemic absorption at cosmetic doses) Preclinical View Profile https://www.bodyhackguide.co/compound/acetyl-hexapeptide-8 ### AHK-Cu Skin & Hair Preclinical AHK-Cu (Ala-His-Lys-Copper) is a copper chelating tripeptide related to but distinct from GHK-Cu (Gly-His-Lys-Copper). t½ Unknown (topical half-life, follicular retention not well characterized) Preclinical View Profile https://www.bodyhackguide.co/compound/ahk-cu ### Melanotan 2 Skin & Hair Discontinued (early clinical) A synthetic melanocortin receptor agonist studied for skin tanning, sexual function, and appetite suppression.. t½ ~1–2 hours 100-1,000 mcg per injection Preclinical View Profile https://www.bodyhackguide.co/compound/melanotan-2 ### Minoxidil Skin & Hair FDA-Approved Minoxidil is an FDA-approved treatment for pattern hair loss. t½ Oral minoxidil plasma half-life is approximately 3-4 hours; the hair-growth (pharmacodynamic) effect is independent of plasma level and depends on ongoing daily use. Oral low-dose minoxidil (off-label): 625-5000 mcg/day (0.625-5 mg). Topical minoxidil is dosed by concentration (2% or 5%), not by mcg -- roughly 10-20 mg of minoxidil is delivered per topical application, with only ~1.4% absorbed systemically. Preclinical View Profile https://www.bodyhackguide.co/compound/minoxidil ### PDRN Skin & Hair Phase 4 PDRN (Polydeoxyribonucleotide) is a biotechnological compound derived from salmon sperm DNA (Oncorhynchus mykiss) through extraction, purification, and fractionation. t½ Short (oligonucleotides degraded rapidly; tissue effects persist longer) Preclinical View Profile https://www.bodyhackguide.co/compound/pdrn ### PTD-DBM Skin & Hair Preclinical PTD-DBM is a synthetic peptide that joins a protein transduction domain, which carries the peptide into cells, to the Dishevelled-binding motif (DBM) of the protein CXXC5, and it was built to block CXXC5 from binding Dishevelled so that Wnt/beta-catenin signalling stays switched on (PMID: 26056233). t½ No published human value, and no published pharmacokinetic study in any species was found. The 2015 report states only that the fluorescein-tagged peptide was delivered into cells in culture and in mouse skin, without plasma or tissue concentrations over time (PMID: 26056233). Preclinical View Profile https://www.bodyhackguide.co/compound/ptd-dbm View Full Dosage Guide → Protocols, calculator & safety for Palmitoyl Pentapeptide-4 https://www.bodyhackguide.co/guides/dosage/palmitoyl-pentapeptide-4 ### Price check No vendor listings yet See the vendor scorecard (https://www.bodyhackguide.co/vendors/scorecard) ### Research Score 45 0 PubMed results ### Quality Indicators Data Completeness 63% Description Mechanism of Action Chemical Data Dosing Protocols Safety Profile PubMed Results Interactions Vendor Listings ### Quick Facts Half-Life Molecular Weight 802.1 g/mol Administration Topical CAS Number Trial Phase Marketed topical cosmetic ingredient with a small set of human cosmetic trials ### Safety Profile Common Side Effects - • Described as well tolerated by the skin at 3 parts per million over 12 weeks in 93 women (PMID: 18492182) - • No adverse event is reported either way in the 21-subject 8-week periorbital trial (PMID: 36909866) - • No adverse event is reported either way in two split-face studies of multi-ingredient products containing it (PMID: 19735523) Research Disclaimer This information is for educational and research purposes only. Not intended as medical advice. Consult a healthcare professional before use. ## Frequently Asked Questions What is palmitoyl pentapeptide-4? Palmitoyl pentapeptide-4 is a cosmetic ingredient made of the five-amino-acid sequence Lys-Thr-Thr-Lys-Ser with a 16-carbon palmitic acid chain attached, abbreviated Pal-KTTKS and sold to formulators as Matrixyl. The peptide part is a copy of residues 212 to 216 of the carboxyl-terminal propeptide of type I collagen, which Katayama and colleagues identified in 1993 as the shortest fragment that still stimulated collagen and fibronectin production in cultured cells (PMID: 8486721). Palmitoyl pentapeptide-4 has the formula C39H75N7O10 and a molecular weight of 802.1 g/mol (PubChem CID 9897237). Is Matrixyl the same as palmitoyl pentapeptide-4, and what is Matrixyl 3000? Matrixyl is a trade name for palmitoyl pentapeptide-4, and PubChem and the FDA substance registry both list Matrixyl as a synonym of that ingredient (PubChem CID 9897237). Matrixyl 3000 is a different mixture: the peptides described in the literature as present in Matrixyl 3000 are palmitoyl tripeptide-1, also written Pal-GHK, and palmitoyl tetrapeptide-7, also written Pal-GQPR, and neither of them is Pal-KTTKS (PMID: 42790608). A separate naming trap is that the INCI name Pentapeptide-4 on its own means the bare peptide KTTKS without the palmitate, a different substance with its own CAS number (PubChem CID 9959565). What human evidence exists for palmitoyl pentapeptide-4? Palmitoyl pentapeptide-4 has a small human evidence base of topical cosmetic trials. The largest trial of palmitoyl pentapeptide-4 is a 12-week, double-blind, placebo-controlled, split-face study in 93 Caucasian women aged 35 to 55 comparing a moisturizer with the same moisturizer containing 3 parts per million of the peptide, which reported significant reduction in wrinkles and fine lines against placebo by image analysis and expert grading, with the peptide well tolerated, and the first author is listed at The Procter and Gamble Company (PMID: 18492182). A 2023 double-blind trial in 21 Indonesian women over eight weeks compared it with acetyl hexapeptide-3 cream and placebo and reported better results for palmitoyl pentapeptide-4, while calling itself an initial study (PMID: 36909866). Two further split-face studies tested multi-ingredient products containing it (PMID: 19735523), and one randomized trial in irradiated skin found no benefit for a three-active cream containing Matrixyl (PMID: 15127162). Does palmitoyl pentapeptide-4 actually get through the skin? Palmitoyl pentapeptide-4 penetrates better than the bare peptide, and not far. In hairless mouse skin, unmodified KTTKS was not detected in any skin layer, while pal-KTTKS was measured at 4.2 micrograms per square centimetre in the stratum corneum, 2.8 in the epidermis and 0.3 in the dermis, and neither form reached the fluid beneath the skin (PMID: 25143811). KTTKS and pal-KTTKS are both degraded quickly by skin enzymes, the palmitoylated one more slowly (PMID: 25143811; PMID: 22921149). A 2011 review of the field flagged the absence of penetration data as a problem for the whole ingredient (PMID: 21535443), and microneedles raised the measured signal in excised human skin by 2 to 22 fold over simple application (PMID: 25033398). Why is the palmitate chain attached to the peptide? The palmitate chain on palmitoyl pentapeptide-4 is there for delivery and potency. Karl Lintner at Sederma published the approach in 2000: attaching a long-chain fatty acid to a peptide improves skin penetration, specific activity and the economics of using it in a product (PMID: 18503476). Work at the University of Reading, with two Procter and Gamble co-authors, added a physical reason the chain matters: pal-KTTKS self-assembles above a critical aggregation concentration into beta-sheet nanotapes, unlike the related palmitoyl peptides Pal-GHK and Pal-KT (PMID: 23822110), and collagen stimulation in fibroblasts rose near that same concentration (PMID: 23320752). Is palmitoyl pentapeptide-4 approved or regulated as a drug? Palmitoyl pentapeptide-4 is not an FDA-approved drug. The ingredient is used under its INCI name in cosmetics and is registered in the FDA substance registry under the identifier KK181SM5JG, which records the substance rather than approving a medicine. A search of the FDA Drugs@FDA database on 20 October 2026 for palmitoyl pentapeptide-4, pal-KTTKS, KTTKS and Matrixyl returned no approved product, and a search of ClinicalTrials.gov the same day returned no registered study under any of those names. What are the known risks of palmitoyl pentapeptide-4? Palmitoyl pentapeptide-4 has a thin but mostly uneventful safety record in topical cosmetic use. The 93-subject trial described palmitoyl pentapeptide-4 as well tolerated by the skin (PMID: 18492182), and neither the trial in Indonesia nor the two split-face product studies make any statement about adverse events (PMID: 36909866; PMID: 19735523). The one trial that recorded adverse events used a three-active cream containing Matrixyl on irradiated skin, where one suspected allergic reaction and more frequent itching occurred in that arm (PMID: 15127162). A 2026 bioinformatic screen by authors with commercial ties to the ingredient found sequence homology with skin matrix proteins and no toxin or allergen flags (PMID: 41953401). The mechanism-level caution is dose direction: in culture, 0.1 micromolar reduced myofibroblast conversion while 0.5 micromolar did not, and the authors said the balance between repair and fibrosis should guide dose (PMID: 30603464). ## Research Tools ### Peptide Calculator Reconstitution & syringe units https://www.bodyhackguide.co/tools/reconstitution ### Reconstitution Guide How to mix, step by step https://www.bodyhackguide.co/guides/how-to-reconstitute-peptides ### Nasal Spray Calc mL per actuation https://www.bodyhackguide.co/tools/intranasal ### Half-Life Visualizer Decay curves https://www.bodyhackguide.co/tools/halflife ## You may also like ### Snap-8 Skin & Hair View product (https://www.bodyhackguide.co/buy/snap-8) ### Acetyl Hexapeptide-8 Skin & Hair View product (https://www.bodyhackguide.co/buy/acetyl-hexapeptide-8) ### AHK-Cu Skin & Hair View product (https://www.bodyhackguide.co/buy/ahk-cu) ### PDRN Skin & Hair View product (https://www.bodyhackguide.co/buy/pdrn) ## Related Compounds ### Acetyl Hexapeptide-8 ### AHK-Cu Skin & Hair Preclinical ### Melanotan 2 ### Minoxidil Skin & Hair FDA-Approved ### PDRN Skin & Hair Phase 4 ### PTD-DBM Skin & Hair Preclinical ## Research Benches Reference pages that put Palmitoyl Pentapeptide-4 next to the compounds people pair it with: roles, evidence, overlap and conflicts. No dosing. Research use only. 01 research bench Peptides for Skin GHK-Cu, palmitoyl pentapeptide-4, acetyl hexapeptide-8 and Snap-8, next to the GLOW and KLOW blends 6 compounds human data on 4 of 6 https://www.bodyhackguide.co/stack/skin-peptides Free 2026 Peptide Cheat Sheet (PDF) 38 compounds and blends: vial sizes, BAC water volumes, dosing ranges and bloodwork markers. Download Free (https://www.bodyhackguide.co/guides/peptide-cheat-sheet-download) ### Need bloodwork before starting? Full hormone + metabolic panels from Anabolic Insights. Code CHONCH for first-order discount. Image: BodyHackGuide (https://www.bodyhackguide.co/assets/bodyhackguide-logo-DOzZNUyh.webp) ### BodyHackGuide Your biohacking research hub: compound pricing, brain health protocols, dosing tools, and vendor reviews. support@bodyhackguide.co Join our Discord: https://discord.gg/Mhq5UdRYBA r/BodyHackGuide on Reddit: https://reddit.com/r/BodyHackGuide #### Explore - Compare prices: https://www.bodyhackguide.co/compare - Vendors: https://www.bodyhackguide.co/vendors - Deals: https://www.bodyhackguide.co/deals - Coupons: https://www.bodyhackguide.co/coupons - Nootropics: https://www.bodyhackguide.co/nootropics - Brain health: https://www.bodyhackguide.co/brain-health - Blog: https://www.bodyhackguide.co/blog - Guides: https://www.bodyhackguide.co/guides #### Tools - Reconstitution: https://www.bodyhackguide.co/tools/reconstitution - Half-life visualizer: https://www.bodyhackguide.co/tools/halflife - COA reader: https://www.bodyhackguide.co/tools/coa - Cost calculator: https://www.bodyhackguide.co/tools/cost-calculator - Stack builder: https://www.bodyhackguide.co/stack-builder - All tools: https://www.bodyhackguide.co/tools #### Trust & vendors - Vendor directory: https://www.bodyhackguide.co/vendors - Trust scorecard: https://www.bodyhackguide.co/vendors/scorecard - Vendor trust badge: https://www.bodyhackguide.co/vendors/get-vetted - Scoring methodology: https://www.bodyhackguide.co/vendors/methodology - Peptide cheat sheet: https://www.bodyhackguide.co/guides/peptide-cheat-sheet-download #### Company - About: https://www.bodyhackguide.co/about - Affiliate disclosure: https://www.bodyhackguide.co/affiliate-disclosure - Editorial standards: https://www.bodyhackguide.co/editorial-standards - Creators: https://www.bodyhackguide.co/creators - Coaches: https://www.bodyhackguide.co/coaches - 1-on-1 coaching: https://www.bodyhackguide.co/coaching - Privacy: https://www.bodyhackguide.co/privacy - Terms: https://www.bodyhackguide.co/terms - Full site directory: https://www.bodyhackguide.co/site-directory **Affiliate Disclosure:** We rank every vendor on the same public, reproducible methodology (https://www.bodyhackguide.co/vendors/methodology), and we earn a commission from purchases made through some of our links at no extra cost to you. Full details in our affiliate disclosure (https://www.bodyhackguide.co/affiliate-disclosure). **Research Disclaimer:** All compounds listed are for laboratory and research purposes only. Not for human consumption. This site does not sell or ship any products. Always consult a qualified healthcare professional and comply with local regulations. © 2026 BodyHackGuide. All rights reserved. · Terms (https://www.bodyhackguide.co/terms) · Privacy (https://www.bodyhackguide.co/privacy) ## Structured data ```json [ { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://www.bodyhackguide.co/" }, { "@type": "ListItem", "position": 2, "name": "Compounds", "item": "https://www.bodyhackguide.co/compare" }, { "@type": "ListItem", "position": 3, "name": "Palmitoyl Pentapeptide-4" } ] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "Palmitoyl Pentapeptide-4", "description": "Palmitoyl pentapeptide-4 is the cosmetic ingredient Pal-KTTKS, a five-amino-acid fragment of the type I collagen propeptide with a 16-carbon palmitic acid chain attached, sold to formulators under the trade name Matrixyl (PubChem CID 9897237; PMID: 8486721). The peptide half, Lys-Thr-Thr-Lys-Ser, was identified in 1993 by Katayama and colleagues at the University of Tennessee as the shortest piece of the collagen propeptide that still stimulated production of collagen I, collagen III and fibronectin in cultured cells, and the palmitoylated version is sold as a Sederma cosmetic ingredient (PMID: 8486721; PMID: 18503476). The human evidence is a small set of topical cosmetic trials, the largest being a 12-week study in 93 women whose first author is at Procter and Gamble, plus one 21-subject trial in Indonesia that compared it against acetyl hexapeptide-3 (PMID: 18492182; PMID: 36909866). Palmitoyl pentapeptide-4 is not an FDA-approved drug, and no study of it is registered on ClinicalTrials.gov, checked on 20 October 2026.", "lastReviewed": "2026-10-21T06:27:56.789Z", "url": "https://www.bodyhackguide.co/compound/palmitoyl-pentapeptide-4", "author": { "@type": "Person", "name": "BioChonch", "url": "https://www.bodyhackguide.co/about", "jobTitle": "Founder & Lead Researcher", "sameAs": [ "https://reddit.com/r/BodyHackGuide", "https://reddit.com/r/BrainHackGuide", "https://reddit.com/r/Biohackingher" ], "worksFor": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" } }, "reviewedBy": { "@type": "Person", "name": "BioChonch", "url": "https://www.bodyhackguide.co/about", "jobTitle": "Founder & Lead Researcher", "sameAs": [ "https://reddit.com/r/BodyHackGuide", "https://reddit.com/r/BrainHackGuide", "https://reddit.com/r/Biohackingher" ], "worksFor": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" } }, "publisher": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" }, "mainContentOfPage": { "@type": "WebPageElement", "cssSelector": "main" }, "about": { "@type": "Drug", "name": "Palmitoyl Pentapeptide-4", "alternateName": [ "Pal-KTTKS", "Matrixyl", "Palmitoyl pentapeptide-3", "Pal-Lys-Thr-Thr-Lys-Ser", "Lipopentapeptide 3", "N2-(1-oxohexadecyl)-L-lysyl-L-threonyl-L-threonyl-L-lysyl-L-serine" ], "description": "Palmitoyl pentapeptide-4 is the cosmetic ingredient Pal-KTTKS, a five-amino-acid fragment of the type I collagen propeptide with a 16-carbon palmitic acid chain attached, sold to formulators under the trade name Matrixyl (PubChem CID 9897237; PMID: 8486721). The peptide half, Lys-Thr-Thr-Lys-Ser, was identified in 1993 by Katayama and colleagues at the University of Tennessee as the shortest piece of the collagen propeptide that still stimulated production of collagen I, collagen III and fibronectin in cultured cells, and the palmitoylated version is sold as a Sederma cosmetic ingredient (PMID: 8486721; PMID: 18503476). The human evidence is a small set of topical cosmetic trials, the largest being a 12-week study in 93 women whose first author is at Procter and Gamble, plus one 21-subject trial in Indonesia that compared it against acetyl hexapeptide-3 (PMID: 18492182; PMID: 36909866). Palmitoyl pentapeptide-4 is not an FDA-approved drug, and no study of it is registered on ClinicalTrials.gov, checked on 20 October 2026.", "activeIngredient": "Palmitoyl Pentapeptide-4", "administrationRoute": "Topical", "mechanismOfAction": "Where the sequence comes from Fibril-forming collagens are made as precursors whose end pieces are cut off outside the cell, and those freed fragments appear to feed back on collagen synthesis. Katayama's group had shown that a subfragment of the carboxyl-terminal propeptide of type I collagen, residues 197 to 241, strongly increased extracellular matrix production in cultured fibroblasts, and in 1993 they dissected that fragment down to the pentapeptide Lys-Thr-Thr-Lys-Ser, residues 212 to 216, as the minimum sequence that still produced potent stimulation of collagen and fibronectin production across several mesenchymal cell types (PMID: 8486721). PubChem labels the unmodified peptide accordingly, as procollagen type I residues 212 to 216 (PubChem CID 9959565). A peptide released from a matrix protein that then signals back to the cells is called a matrikine, and a 2011 paper setting out that concept names KTTKS as its example (PMID: 21692860). What it does to cells The measured effect is matrix synthesis, not muscle relaxation or pigment control. A 2011 review of the published work concluded there is a sound in vitro basis for an effect on fibroblasts, with the stimulation specific to collagen types I and III and to fibronectin (PMID: 21535443). In human dermal and corneal fibroblasts, the palmitoylated form raised collagen production in a concentration-dependent way (PMID: 23320752). Designed variants built on the same motif raise collagen and fibronectin in human adipose-derived stem cells (PMID: 28467727), and an acetylated analogue increased collagen synthesis in fibroblasts by about 80 percent in culture (PMID: 27184584). Conjugates that attach the peptide to lipoic acid or to ascorbic acid stimulate collagen more than either part alone in cell culture (PMID: 24090916; PMID: 19944016). Why the palmitate tail is there The peptide alone is small, water-loving and charged, which is poor for crossing the stratum corneum. Karl Lintner at Sederma published the general approach in 2000: long-chain fatty acid conjugates improve skin penetration, specific activity and economic feasibility for peptide actives (PMID: 18503476). Physical chemistry work at the University of Reading, with two Procter and Gamble co-authors, showed the consequence. The palmitoylated peptide self-assembles above a critical aggregation concentration into flat tapes and fibres with high beta-sheet content, which the related palmitoyl peptides Pal-GHK and Pal-KT do not form in the same way (PMID: 23822110), and collagen stimulation in fibroblasts tracked concentration close to that critical aggregation concentration, which the authors read as self-assembly and activity being linked (PMID: 23320752). The chain-length series C14, C16 and C18 was studied on the same assumption, that the lipid chain acts as a prodrug handle and the peptide is released by enzymes in skin (PMID: 22834769). How far it actually gets into skin This is the weak point of the whole class, and the published measurements are modest. The 2011 review noted a surprising absence of in vitro skin penetration data at that time (PMID: 21535443). A 2014 Korean study measured both forms in hairless mouse skin: both were rapidly degraded in skin extracts and homogenates, with the palmitoylated form the more stable of the two, and protease inhibitors improved both. Neither compound reached the receptor fluid under the mouse skin. Unmodified KTTKS was not detected in any skin layer, while pal-KTTKS was found at 4.2 plus or minus 0.7 micrograms per square centimetre in the stratum corneum, 2.8 plus or minus 0.5 in the epidermis and 0.3 plus or minus 0.1 in the dermis (PMID: 25143811). A separate method paper showed the free peptide is cleaved quickly by aminopeptidases in rat skin homogenate (PMID: 22921149). In excised human skin, microneedles raised the fluorescence signal from pal-KTTKS and two other cosmetic peptides by 2 to 22 fold over passive application (PMID: 25033398). A dose-direction finding worth knowing More is not simply better in the one study that looked for a turning point. In human fibroblast cultures and collagen lattices, pal-KTTKS at 0.1 micromolar halved the proportion of cells carrying alpha-smooth muscle actin stress fibres, from 75 plus or minus 7.1 percent to 38.6 plus or minus 16.1 percent, which the authors read as less conversion of fibroblasts into the myofibroblasts that drive scarring; at 0.5 micromolar the effect was not significant. They concluded that the balance between wound-healing and pro-fibrotic actions has to be considered when choosing a dose (PMID: 30603464). Names that get mixed up Three naming traps run through the market copy. First, the INCI name Pentapeptide-4 means the bare peptide KTTKS, while Palmitoyl pentapeptide-4 means the palmitoylated version, and the same palmitoylated molecule was called Palmitoyl pentapeptide-3 under older nomenclature (PubChem CID 9897237; PubChem CID 9959565). Second, the 2011 review points out that KTTKS became loosely associated with the word pentapeptide in cosmetic copy even though many unrelated five-residue peptides exist (PMID: 21535443). Third, Matrixyl and Matrixyl 3000 are not the same thing: the peptides described in the literature as present in Matrixyl 3000 are palmitoyl tripeptide-1 (Pal-GHK) and palmitoyl tetrapeptide-7 (Pal-GQPR), neither of which is Pal-KTTKS (PMID: 42790608).", "legalStatus": "Cosmetic ingredient" } }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "What is palmitoyl pentapeptide-4?", "acceptedAnswer": { "@type": "Answer", "text": "Palmitoyl pentapeptide-4 is a cosmetic ingredient made of the five-amino-acid sequence Lys-Thr-Thr-Lys-Ser with a 16-carbon palmitic acid chain attached, abbreviated Pal-KTTKS and sold to formulators as Matrixyl. The peptide part is a copy of residues 212 to 216 of the carboxyl-terminal propeptide of type I collagen, which Katayama and colleagues identified in 1993 as the shortest fragment that still stimulated collagen and fibronectin production in cultured cells (PMID: 8486721). Palmitoyl pentapeptide-4 has the formula C39H75N7O10 and a molecular weight of 802.1 g/mol (PubChem CID 9897237)." } }, { "@type": "Question", "name": "Is Matrixyl the same as palmitoyl pentapeptide-4, and what is Matrixyl 3000?", "acceptedAnswer": { "@type": "Answer", "text": "Matrixyl is a trade name for palmitoyl pentapeptide-4, and PubChem and the FDA substance registry both list Matrixyl as a synonym of that ingredient (PubChem CID 9897237). Matrixyl 3000 is a different mixture: the peptides described in the literature as present in Matrixyl 3000 are palmitoyl tripeptide-1, also written Pal-GHK, and palmitoyl tetrapeptide-7, also written Pal-GQPR, and neither of them is Pal-KTTKS (PMID: 42790608). A separate naming trap is that the INCI name Pentapeptide-4 on its own means the bare peptide KTTKS without the palmitate, a different substance with its own CAS number (PubChem CID 9959565)." } }, { "@type": "Question", "name": "What human evidence exists for palmitoyl pentapeptide-4?", "acceptedAnswer": { "@type": "Answer", "text": "Palmitoyl pentapeptide-4 has a small human evidence base of topical cosmetic trials. The largest trial of palmitoyl pentapeptide-4 is a 12-week, double-blind, placebo-controlled, split-face study in 93 Caucasian women aged 35 to 55 comparing a moisturizer with the same moisturizer containing 3 parts per million of the peptide, which reported significant reduction in wrinkles and fine lines against placebo by image analysis and expert grading, with the peptide well tolerated, and the first author is listed at The Procter and Gamble Company (PMID: 18492182). A 2023 double-blind trial in 21 Indonesian women over eight weeks compared it with acetyl hexapeptide-3 cream and placebo and reported better results for palmitoyl pentapeptide-4, while calling itself an initial study (PMID: 36909866). Two further split-face studies tested multi-ingredient products containing it (PMID: 19735523), and one randomized trial in irradiated skin found no benefit for a three-active cream containing Matrixyl (PMID: 15127162)." } }, { "@type": "Question", "name": "Does palmitoyl pentapeptide-4 actually get through the skin?", "acceptedAnswer": { "@type": "Answer", "text": "Palmitoyl pentapeptide-4 penetrates better than the bare peptide, and not far. In hairless mouse skin, unmodified KTTKS was not detected in any skin layer, while pal-KTTKS was measured at 4.2 micrograms per square centimetre in the stratum corneum, 2.8 in the epidermis and 0.3 in the dermis, and neither form reached the fluid beneath the skin (PMID: 25143811). KTTKS and pal-KTTKS are both degraded quickly by skin enzymes, the palmitoylated one more slowly (PMID: 25143811; PMID: 22921149). A 2011 review of the field flagged the absence of penetration data as a problem for the whole ingredient (PMID: 21535443), and microneedles raised the measured signal in excised human skin by 2 to 22 fold over simple application (PMID: 25033398)." } }, { "@type": "Question", "name": "Why is the palmitate chain attached to the peptide?", "acceptedAnswer": { "@type": "Answer", "text": "The palmitate chain on palmitoyl pentapeptide-4 is there for delivery and potency. Karl Lintner at Sederma published the approach in 2000: attaching a long-chain fatty acid to a peptide improves skin penetration, specific activity and the economics of using it in a product (PMID: 18503476). Work at the University of Reading, with two Procter and Gamble co-authors, added a physical reason the chain matters: pal-KTTKS self-assembles above a critical aggregation concentration into beta-sheet nanotapes, unlike the related palmitoyl peptides Pal-GHK and Pal-KT (PMID: 23822110), and collagen stimulation in fibroblasts rose near that same concentration (PMID: 23320752)." } }, { "@type": "Question", "name": "Is palmitoyl pentapeptide-4 approved or regulated as a drug?", "acceptedAnswer": { "@type": "Answer", "text": "Palmitoyl pentapeptide-4 is not an FDA-approved drug. The ingredient is used under its INCI name in cosmetics and is registered in the FDA substance registry under the identifier KK181SM5JG, which records the substance rather than approving a medicine. A search of the FDA Drugs@FDA database on 20 October 2026 for palmitoyl pentapeptide-4, pal-KTTKS, KTTKS and Matrixyl returned no approved product, and a search of ClinicalTrials.gov the same day returned no registered study under any of those names." } }, { "@type": "Question", "name": "What are the known risks of palmitoyl pentapeptide-4?", "acceptedAnswer": { "@type": "Answer", "text": "Palmitoyl pentapeptide-4 has a thin but mostly uneventful safety record in topical cosmetic use. The 93-subject trial described palmitoyl pentapeptide-4 as well tolerated by the skin (PMID: 18492182), and neither the trial in Indonesia nor the two split-face product studies make any statement about adverse events (PMID: 36909866; PMID: 19735523). The one trial that recorded adverse events used a three-active cream containing Matrixyl on irradiated skin, where one suspected allergic reaction and more frequent itching occurred in that arm (PMID: 15127162). A 2026 bioinformatic screen by authors with commercial ties to the ingredient found sequence homology with skin matrix proteins and no toxin or allergen flags (PMID: 41953401). The mechanism-level caution is dose direction: in culture, 0.1 micromolar reduced myofibroblast conversion while 0.5 micromolar did not, and the authors said the balance between repair and fibrosis should guide dose (PMID: 30603464)." } } ] }, { "@context": "https://schema.org", "@type": "Organization", "@id": "https://www.bodyhackguide.co#organization", "name": "BodyHackGuide", "alternateName": "BHG", "url": "https://www.bodyhackguide.co", "logo": { "@type": "ImageObject", "url": "https://www.bodyhackguide.co/logo.png", "width": 512, "height": 512 }, "description": "Evidence-based research reference for peptides and nootropics. 273 compound profiles, interactive dosing calculators, vendor price comparisons, and trust-scored vendor reviews scored on a public, reproducible methodology applied to every vendor. We earn a commission on purchases through some of our links.", "foundingDate": "2024", "founder": { "@id": "https://www.bodyhackguide.co/about#person" }, "sameAs": [ "https://reddit.com/r/BodyHackGuide", "https://reddit.com/r/BrainHackGuide", "https://reddit.com/r/Biohackingher", "https://discord.gg/Mhq5UdRYBA" ], "knowsAbout": [ "Peptide research", "Nootropic research", "Biohacking", "Compound dosing", "Vendor transparency" ], "publishingPrinciples": "https://www.bodyhackguide.co/editorial-standards", "ethicsPolicy": "https://www.bodyhackguide.co/editorial-standards", "diversityPolicy": "https://www.bodyhackguide.co/editorial-standards" } ] ```