Acetyl Dipeptide-1 Cetyl Ester (Calmosensine)_Dosage, benefits & legal status
Also known as Calmosensine, Calmosensine SP, Calmosensine 1 SP, acetyl dipeptide-1, Ac-Tyr-Arg-O-hexadecyl, N-acetyl-L-tyrosyl-L-arginine hexadecyl ester
A two-residue peptide with a 16-carbon tail, sold by Sederma as Calmosensine to make skin sting less. It was the most-used peptide in a 2021 survey of 88 sensitive-skin facial products, and the only peer-reviewed human study of it was run by a competitor.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Acetyl Dipeptide-1 Cetyl Ester (Calmosensine)?
Plain language first. The technical label stays, but it never stands alone.Overview
If you use anything sold for sensitive or easily stung skin, you may already be using it: a 2021 review of 88 facial products found it in more than 5% of them, more than any other peptide. The only peer-reviewed human test is a 31-woman split-face capsaicin study run by Beiersdorf researchers promoting a rival ingredient; their product soothed faster and more strongly at the early time points, the two matched at the peak of burning, and the 2021 review read that result as no significant effect for this peptide. Everything else is supplier panel data: 21 volunteers rating levels of heat and 18 rating comfort after sandpaper abrasion, neither of them published.
Acetyl dipeptide-1 cetyl ester is N-acetyl-L-tyrosyl-L-arginine hexadecyl ester: the dipeptide Tyr-Arg with an acetyl cap on the tyrosine's amino end and a 16-carbon cetyl chain esterified to the arginine's carboxyl end, C33H57N5O5 at 603.8 daltons. Sederma, now part of Croda, filed the originating patent in 1996 and sells it as Calmosensine; the proposed mechanism is release of one of the body's own opioid peptides in skin, damping release of the sensory neuropeptide CGRP and so reducing TRPV1-driven stinging. The supplier's own sources name two different opioid peptides for that step, beta-endorphin by way of the POMC gene in one place and met-enkephalin in another, and neither version has published human skin data behind it.
What it's used for
A cosmetic ingredient in creams, serums and some shampoos and conditioners, aimed at skin that stings, reddens or feels tight. Used only on the skin.
How does Acetyl Dipeptide-1 Cetyl Ester (Calmosensine) work?
What it does in the body, and where.The chain of reasoning runs from a fatty tail carrying a small dipeptide into the skin to an opioid signal that quiets stinging nerves; the first step is chemistry, and the rest is supplier documentation.
- 01A dipeptide with a tailThe molecule is the dipeptide Tyr-Arg with an acetyl cap at one end and a 16-carbon cetyl chain esterified to the other. That chain makes a small, water-loving peptide greasy enough to sit in the outer skin, and the ester bond can in principle be cut by skin esterases to free the acetylated dipeptide. No penetration, stability or esterase data for this molecule have been published.
- 02An opioid step nobody has shownSederma's material says the dipeptide prompts skin cells or nerve endings to release one of the body's own opioid peptides. The 2021 review reports it as switching on the POMC gene, whose product beta-endorphin would be that opioid; an ingredient database reports met-enkephalin instead, a peptide made from a different precursor. The two versions name different opioid peptides made from different precursors, and no peer-reviewed human skin data support either.
- 03Less CGRP, less stingingThe proposed end of the chain is that the opioid damps release of CGRP from sensory nerves, so the heat and capsaicin receptor TRPV1 drives less burning, stinging and redness. In the 2021 review the citation after the TRPV1 statement is a Sederma brochure rather than a research paper, and the beta-endorphin and CGRP step carries no citation at all. A separate line of in vitro work reports more barrier proteins in cultured skin cells, from an industry study that tested the single active, and the formula it belongs to, with no volunteers.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
The only peer-reviewed human study
tested-and-failed- Human trial31 women aged 19 to 65 with sensitive skin, randomized, single-blind, split-face capsaicin stinging test: the 4-t-butylcyclohexanol comparator soothed faster and more strongly early, and the two products did not differ at the peak of burning.
- No dataAll five authors were Beiersdorf research staff, and Beiersdorf sells sensitive-skin products built on the comparator. The paper appeared in a journal supplement next to a second Beiersdorf paper on that same ingredient.
- No dataThe 2021 review reports this study as showing no significant effect for the peptide and presents that as the study authors' own conclusion. The abstract does not state it, and the full text is paywalled. No trial registry entry for the study was found.
Supplier panel data
Supplement or cosmetic- human-earlyA cream containing 3% acetyl dipeptide-1 cetyl ester was tested on 21 volunteers asked to tell four levels of heat apart; heat perception fell significantly at the hot, very hot and painful levels. No statistics, control description or publication accompanies it.
- No dataA double-blind panel of 18 volunteers compared a treated hand with an untreated hand after sandpaper abrasion and reported greater comfort, measured with a lie detector. That is a non-standard way to measure comfort, and the test is unpublished.
- No dataThe 1996 patent reports its own in vivo test in 20 volunteers with reduced heat sensitivity against placebo. The patent says 20 and the review says 21, so these may be the same panel reported twice.
Cell and tissue work
Early research- Lab studyIn primary human keratinocytes the compound was reported to raise aquaporin-3, filaggrin, caspase-14 and keratin-10, and, like niacinamide tested on its own, to raise dermal genes including COL1A1, fibrillin-1, decorin and LOXL1.
- No dataThat study had no clinical or volunteer arm, tested the ingredient on its own as one of four actives being developed into a commercial formula, and all eight authors worked for Oriflame Cosmetics, the company behind the product.
- No dataA reagent catalog repeats those gene results as settled properties of the compound and adds an effect on glyoxal-driven advanced glycation end products in fibroblasts; in that same paper that result belongs to the complete formula, not to the peptide.
How widely it is used
Supplement or cosmetic- ReviewOf 88 facial cosmetics for sensitive skin, 15 (about 17%) contained peptides and 7 distinct peptides appeared; this one was the most used, present in more than 5% of all the products sampled.
- ReviewAn ingredient database lists it in more than 50 marketed products, including several L'Oreal Revitalift Laser items, more than a dozen Ecoforia face and hair products, and items from La Roche-Posay, Ahava, Sesderma and others. These databases are user-built and incomplete.
- ReviewIt was the only one of the 7 peptides with a human study in volunteers who had sensitive skin, and that study is the negative comparison above.
It is often described loosely as an acetylated dipeptide derivative. The detail matters: the acetyl group caps the tyrosine at the front, and the 16-carbon chain hangs off the arginine at the back through an ester bond, unlike the palmitoyl peptides on this site, where the fatty chain sits at the front as an amide. The evidence behind it is reported as ingredient studies plus limited human testing; the accurate version is one peer-reviewed human study, run by a competitor, in which this peptide did not come out ahead, plus two unpublished supplier panels. That review is cited for a claim that this peptide cuts prostaglandin E2 and NF-kB signaling, but the paper it cites for that is about 4-t-butylcyclohexanol and licochalcone A, two other ingredients. The trade product is often described as a solution in glycerin and water; Croda publishes it as butylene glycol, water, Laureth-3, hydroxyethylcellulose and the peptide, with the peptide concentration undisclosed. Supplier copy gives two incompatible opioid mechanisms, beta-endorphin by way of POMC in one place and met-enkephalin in another, and neither has human skin data. A reagent catalog presents the keratinocyte gene results as properties of the compound, when they come from one industry study of a single active in cell culture with no volunteers. The parent dipeptide Tyr-Arg is the same pair of residues as kyotorphin, a peptide found in brain tissue, but that is a structural observation: neither Sederma nor the review calls it that, and no published work shows this ester reproduces kyotorphin's pharmacology in skin. Calling it a proprietary Sederma peptide now describes only the trade product, since the original patent family has lapsed.
The published record
Papers and trials about Acetyl Dipeptide-1 Cetyl Ester (Calmosensine)
4 papers tagged human · 2 not reviews or lab · 2 clinical trial publications
Furthest stage reached: Published trials only, 2 clinical trial publications, no phased trial registered
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about Acetyl Dipeptide-1 Cetyl Ester (Calmosensine)
Evidence
Cosmetic
Category
Skin and cosmetic
Common vial
Varies
Half-life
Not established
How much, and do you cycle it?
The range, and whether you take breaks.Use level not public; 2% in the patent's concentrate solution, about 0.1% in its example cream and 3% in a cream the supplier tested (patent and 2021 review), daily. Daily use Community practice
Applied daily like other cosmetic actives. No study has tested a schedule; the one published human test measured stinging over a single session.
Not establishedNo figure
Applied to the skin. No half-life, absorption, penetration, metabolism or clearance data exist for this molecule. The 16-carbon chain is there to raise fat solubility, and the ester bond could in principle be cut by skin esterases to release the acetylated dipeptide, but neither step has been shown. For the parent dipeptide kyotorphin, a 2017 review reports fast breakdown by two brain aminopeptidases and poor passage into the brain; that is kyotorphin, not this ester.
You can compare this against the whole library to see where it sits.
What does it cost?
Typical dose and cost, in plain numbers.Acetyl Dipeptide-1 Cetyl Ester (Calmosensine) is not injected
It is taken on the skin (cream or serum). A leave-on cosmetic ingredient in creams, serums and some hair products. Croda's recommended use level for Calmosensine SP sits behind a supplier login, and the peptide content of the trade solution is not disclosed either, so the amount of peptide in a finished product cannot be worked out and the calculator has no range to draw. The trade product is the peptide dissolved in butylene glycol and water with Laureth-3 and hydroxyethylcellulose, with the peptide listed last. A second supplier sells a 0.3% solution, 3,000 parts per million, and a powder above 95% purity. The patent's Example 1 is a 2% solution of the compound in glycols, and its Example 3 cream contains 5% of that solution, about 0.1% peptide; the 2021 review separately describes a cream as 3% acetyl dipeptide-1 cetyl ester, without saying whether that 3% is the peptide or the trade solution. There is no oral or injected dose.
How do you store it?
Before mixing, and after.Room temperature, out of light. Cap it tight after each use.
Acetyl Dipeptide-1 Cetyl Ester (Calmosensine) ships as a cream, gel, or serum. Keep it at room temperature away from sun and heat unless the label says otherwise. Refrigerating an emulsion can split the texture. Watch for color, smell, or separation changes and stop using it if any appear.
What are the side effects and cautions?
Known cautions and warnings for this compound.Who should avoid it
- Not studied in men: the one peer-reviewed study enrolled 31 women aged 19 to 65 with sensitive skin
- Not studied in children, pregnancy or breastfeeding: no data of any kind have been published
- Not studied by mouth or by injection: it is sold as a cosmetic raw material and as a laboratory reagent, and no study has looked at what it does inside the body
- Known sensitivity to a product that contains it
Stop and get help
- Redness, burning, itching or a rash where it is applied
Common effects
- No side effects appear in the abstract of the 31-woman capsaicin study, whose full text is paywalled, or in the summaries of the 21-volunteer heat panel and the 18-volunteer abrasion panel, and none of the three published a safety table
- No repeated patch test, irritation or sensitization study has been published, and no Cosmetic Ingredient Review safety assessment was found
- It is listed in more than 50 marketed products, including several L'Oreal Revitalift Laser items and several La Roche-Posay Toleriane items, with no reported pattern of complaints
- Laboratory suppliers sell the raw compound with research-only disclaimers that say nothing about cosmetic safety
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Acetyl Dipeptide-1 Cetyl Ester (Calmosensine) approved?
And where the numbers on this page come from.Not as a medicine. Acetyl Dipeptide-1 Cetyl Ester (Calmosensine) is sold without a prescription as a cosmetic ingredient, which is a different thing from being approved as a drug.
- Approval statusCosmeticSold without a prescription as an ingredient in cosmetics, such as skincare and hair products. The FDA does not approve cosmetics before they are sold, and being easy to buy says nothing about whether it works.
- RouteOn the skin (cream or serum)
- Checked21 October 2026
- DoseFrom the concentration range manufacturers formulate at. This is a product strength, not a dose set by a regulator or a trial.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesFDA GSRS substance record, acetyl dipeptide-1 cetyl ester (UNII 3M7W78X5IR)FDA GSRS substance record, kyotorphin (UNII 02N30CW3X0)Sederma patent WO 98/07744 (Greff)Croda Beauty, Calmosensine SP product pageSpecialChem technical datasheet, Calmosensine SPResende DISP et al., Pharmaceuticals 2021;14:702Schoelermann AM et al., Journal of the European Academy of Dermatology and Venereology 2016;30(Suppl 1):18-20Sulzberger M et al., JEADV 2016;30(Suppl 1):9-17 (title record)Khmaladze I et al., Journal of Cosmetic Dermatology 2020;19:1415-1425Cayman Chemical, acetyl dipeptide-1 cetyl ester trifluoroacetate salt (item 34949)Active Peptide Company listing (UL Prospector)COSMILE Europe, entry 229INCIDecoder, acetyl dipeptide-1 cetyl esterPerazzo J, Castanho MARB, Sa Santos S, Frontiers in Pharmacology 2017;7:530
What has happened recently
A cosmetic ingredient, not a drug, and never submitted as one: no approval or designation exists anywhere, no international nonproprietary name has been assigned, and no clinical trial registration was found under the ingredient name, the trade name or the chemical name. FDA's substance registry gives it UNII 3M7W78X5IR, CAS 196604-48-5, the formula C33H57N5O5 and a full stereospecific structure. Databases that mirror the EU cosmetic ingredient inventory, including COSMILE Europe (entry 229) and INCIDecoder, report its declared functions as hair conditioning and skin conditioning with no restriction; the EU record itself could not be read. The name is an INCI name, assigned by the Personal Care Products Council, so a dictionary monograph is implied rather than seen, and no Cosmetic Ingredient Review safety assessment was found. Croda states that Calmosensine SP complies with China's inventory of existing cosmetic ingredients and lists it as halal and vegan suitable, sold in Asia, Europe, Latin America and North America. Sederma SA filed the originating patent on August 23, 1996 with Daniel Greff as sole inventor, published as WO 98/07744 on February 26, 1998, with US 6,372,717 and EP 0920445 in the same family; Google Patents lists the application as ceased and the granted US and EP patents as expired, so the composition protection has lapsed and second-source suppliers now sell the raw material. Research-grade material is sold as a lab reagent, not for human use.
You can compare this against the whole library, or read how to check a seller.
What else is like Acetyl Dipeptide-1 Cetyl Ester (Calmosensine)?
Others in Skin and cosmetic, side by side.If you're weighing Acetyl Dipeptide-1 Cetyl Ester (Calmosensine), it's worth reading Acetyl Hexapeptide-37 (Diffuporine), Acetyl Tetrapeptide-11, and Acetyl Tetrapeptide-15 (Skinasensyl) in the same class.
A two-residue peptide with a 16-carbon tail, sold by Sederma as Calmosensine to make skin sting less. It was the most-used peptide in a 2021 survey of 88 sensitive-skin facial products, and the only peer-reviewed human study of it was run by a competitor.
- Dose
- Use level not public; 2% in the patent's concentrate solution, about 0.1% in its example cream and 3% in a cream the supplier tested (patent and 2021 review)
- How often
- Daily
A six-residue Lipotec peptide sold as Diffuporine, said to make skin cells produce more aquaporin-3 water channels. Every efficacy figure comes from the supplier, with methods undisclosed.
- Dose
- 2% Diffuporine solution in a cream or serum (supplier)
- How often
- Per product; no tested schedule published
A topical cosmetic peptide sold as Syniorage, claimed to firm mature skin by raising syndecan-1 and collagen XVII.
- Dose
- Serum or cream, per product
- How often
- Daily
An acetyl-capped copy of endomorphin-2, an opioid peptide, sold by BASF as Skinasensyl to make reactive skin less easily irritated. Its only data are supplier tests published without numbers.
- Dose
- BASF use level not public; 0.0015% in the supplier's volunteer test (2021 review)
- How often
- Twice daily (supplier test)
Guides for this compound
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- FDA GSRS substance record, acetyl dipeptide-1 cetyl ester (UNII 3M7W78X5IR)(2026)Canonical structure Ac-L-Tyr-L-Arg-O-hexadecyl with both stereocenters defined as L; C33H57N5O5, MW 603.8374; CAS 196604-48-5; registered as a chemical rather than a protein, with no peptide modifications recorded.
- FDA GSRS substance record, kyotorphin (UNII 02N30CW3X0)(2026)Kyotorphin is L-tyrosyl-L-arginine, C15H23N5O4, MW 337.3748: the same two residues as the parent dipeptide of this ingredient, without the acetyl cap or the ester.
- Sederma patent WO 98/07744 (Greff)(1998)Filed August 23, 1996 and published February 26, 1998, assigned to Sederma SA; claim 4 names N-acetyl-L-Tyr-L-Arg-O-hexadecyl; melting point 140 to 143 degrees Celsius; 2% of the compound in the Example 1 concentrate solution, 5% of which goes into the Example 3 cream, about 0.1% peptide; an in vivo test in 20 volunteers reporting reduced heat sensitivity against placebo; the PCT application listed as ceased and US 6,372,717 and EP 0920445 listed as expired.
- Croda Beauty, Calmosensine SP product page(2026)Trade product listed as butylene glycol, water, Laureth-3, hydroxyethylcellulose and acetyl dipeptide-1 cetyl ester; headline claim that it modulates perception of unpleasant sensations; applications from after-sun to leg care; halal and vegan suitable; compliant with China's ingredient inventory. No use level is published.
- SpecialChem technical datasheet, Calmosensine SP(2020)Same composition, described as a lipopeptide solubilized in a hydroglycolic excipient; the recommended use level is visible only after login.
- Resende DISP et al., Pharmaceuticals 2021;14:702(2021)Of 88 facial products for sensitive skin, 15 (about 17%) contained peptides and 7 distinct peptides appeared; this one was the most used, in more than 5% of all products. Reports the POMC claim, the 3% cream, the 21-volunteer heat panel and the 18-volunteer sandpaper panel from supplier brochures, says most information on these ingredients is not in peer-reviewed journals, and reads the 2016 human study as showing no significant effect for this peptide.
- Schoelermann AM et al., Journal of the European Academy of Dermatology and Venereology 2016;30(Suppl 1):18-20(2016)The only peer-reviewed human study: 31 women aged 19 to 65 with sensitive skin, randomized, single-blind, split-face capsaicin stinging test. Both products reduced burning, the 4-t-butylcyclohexanol product acted faster and more strongly early, and the two did not differ at the point of most intense burning. All five authors worked in research and development at Beiersdorf.
- Sulzberger M et al., JEADV 2016;30(Suppl 1):9-17 (title record)(2016)The paper the 2021 review cites for a prostaglandin E2 and NF-kB effect is about 4-t-butylcyclohexanol and licochalcone A, not about this peptide.
- Khmaladze I et al., Journal of Cosmetic Dermatology 2020;19:1415-1425(2020)More aquaporin-3, filaggrin, caspase-14 and keratin-10 in primary human keratinocytes, and, like niacinamide tested separately, more dermal genes including COL1A1, fibrillin-1, decorin and LOXL1. In vitro and ex vivo only, inside a multi-ingredient commercial formula; all eight authors worked for Oriflame Cosmetics.
- Cayman Chemical, acetyl dipeptide-1 cetyl ester trifluoroacetate salt (item 34949)(2026)Sold as the trifluoroacetate salt at 98% or better for research use only; the formal name confirms the structure; the page repeats the keratinocyte gene claims and adds a reduction in glyoxal-driven advanced glycation end products in fibroblasts, citing the same single paper, in which that anti-glycation result belongs to the complete multi-active formula rather than the peptide.
- Active Peptide Company listing (UL Prospector)(2026)A second-source cosmetic raw material: a 0.3% solution, stated as 3,000 parts per million, and a powder above 95% purity, with custom concentrations on request.
- COSMILE Europe, entry 229(2026)Declared cosmetic functions hair conditioning and skin conditioning; origin synthetic.
- INCIDecoder, acetyl dipeptide-1 cetyl ester(2026)Trade name Calmosensine; gives met-enkephalin as the released opioid peptide; lists more than 50 finished products across several paginated pages, including several L'Oreal Revitalift Laser items, more than a dozen Ecoforia face and hair products and several La Roche-Posay Toleriane items. The database is user-built.
- Perazzo J, Castanho MARB, Sa Santos S, Frontiers in Pharmacology 2017;7:530(2017)Kyotorphin, isolated from bovine brain in 1979 and named for Kyoto, does not bind opioid receptors directly but acts by releasing met-enkephalin; it is broken down fast by two brain aminopeptidases and crosses into the brain poorly, the reason peptidase-resistant derivatives were made.
Beyond these, 5 records are indexed. Browse the records