Rigin

Sederma's trade name for palmitoyl tetrapeptide-7 (Pal-GQPR, CAS 221227-05-0), a palmitoylated fragment of human immunoglobulin G used in topical cosmetics for reported IL-6-modulating, skin-soothing effects and best known as half of the Matrixyl 3000 blend.

Also referenced as: Palmitoyl Tetrapeptide-7, Palmitoyl Tetrapeptide-3, Pal-GQPR, Pal-Gly-Gln-Pro-Arg

Also appears in: Longevity · Immune

What is Rigin?

The name “Rigin” belongs to two closely related molecules, and the history matters. The original rigin is the free tetrapeptide Gly-Gln-Pro-Arg (GQPR). Structure-function and conformational work on tuftsin predicted that trypsin digestion of the human IgG heavy chain should release a second, tuftsin-like tetrapeptide with a similar spatial arrangement; GQPR was then synthesized and its phagocytosis-stimulating activity was found equal to tuftsin’s (Veretennikova et al., Int J Pept Protein Res, 1981;17(4):430-435). The two peptides come from the same heavy chain but different stretches of it — tuftsin is residues 289-292, while rigin is conventionally numbered Gly341-Gln-Pro-Arg344.

In today’s market, Rigin is Sederma’s (Croda) trade name for palmitoyl tetrapeptide-7 — the same GQPR sequence conjugated to palmitic acid (Pal-Gly-Gln-Pro-Arg, CAS 221227-05-0) for skin compatibility and formulation stability. The palmitoylated form appears in the research-peptide and cosmetic markets mainly as one half of the Matrixyl 3000 blend, paired with palmitoyl tripeptide-1 (Pal-GHK), and secondarily as a standalone “soothing” anti-aging ingredient.

How it works

• The parent sequence GQPR is an immunomodulatory antibody fragment. It was reached by conformational analysis rather than by screening: theoretical modeling showed the tetrapeptide’s spatial arrangement closely resembled tuftsin’s, which is why it was predicted to carry tuftsin-like activity — and the synthesized peptide’s phagocytosis-stimulating potency matched tuftsin’s when tested (Veretennikova et al., Int J Pept Protein Res, 1981;17(4):430-435).
• The cosmetic mechanism claimed for palmitoyl tetrapeptide-7 is anti-inflammatory matrix protection: reduced IL-6 secretion, a damped inflammatory response after UVB exposure, and increased production of the basement-membrane proteins laminin IV and laminin V plus collagen VII. A 2021 peer-reviewed review repeats those effects and classifies the ingredient as a signal peptide, but it sources them to the Sederma-authored Mondon paper rather than to independent primary work (Resende et al., Pharmaceuticals (Basel), 2021;14(8):702).
• IL-6 is a pro-inflammatory cytokine implicated in chronic, low-grade degradation of the dermal extracellular matrix; the design rationale within Matrixyl 3000 is complementary action — Pal-GHK as a collagen-stimulating signal peptide, Pal-GQPR as an inflammation-damping partner. That pairing logic is supplier positioning, not a tested hypothesis: no published study compares the blend against either peptide alone.
• Palmitoylation exists to help an otherwise hydrophilic peptide associate with the lipid-rich stratum corneum. The standard reference on this class of ingredient sorts cosmetic peptides into signal, enzyme-inhibitor, neurotransmitter-inhibitor and carrier peptides and reviews the controlled ex vivo and in vivo efficacy studies behind each (Gorouhi & Maibach, Int J Cosmet Sci, 2009;31(5):327-345); how much intact peptide actually crosses the barrier from a finished product remains the field’s recurring open question.
• Independent of the cosmetic lane, hydrophobic rigin analogs improved both cell-mediated and humoral immune responses in mice and, dosed prophylactically by intravenous injection, reduced parasitaemia and mortality after a Plasmodium berghei challenge (Dutta et al., Int Immunopharmacol, 2001;1(5):843-855). Read the structures before importing this as support for the cosmetic ingredient: those analogs carry their hydrophobic group at the C-terminus — an N-palmitoyl-amino-ethyl amide, plus a cholestanyl version that performed better — not the N-terminal palmitoylation of Pal-GQPR, and the response ran through lymphocytes rather than the macrophage route tuftsin uses.

Research status

No interventional study on ClinicalTrials.gov tests palmitoyl tetrapeptide-7 as the agent under investigation. The single registry record that mentions the ingredient at all is NCT05932732, a completed HydraFacial device trial in which the peptide sits inside a booster serum rather than under test — exactly the incidental pattern you would expect for a cosmetic raw material. Searching the registry for “rigin” or “palmitoyl tetrapeptide-3” returns nothing.

The human data that exists comes from multi-ingredient cosmetic studies. Mondon et al., J Cosmet Dermatol, 2015;14(2):152-160 — a Sederma-authored study whose stated purpose was to establish a MALDI mass-spectrometric imaging methodology for dermal matrix and epidermal-dermal junction proteins — included an anti-aging arm using a blend of palmitoyl oligopeptide and palmitoyl tetrapeptide-7. In that arm, echography showed reduced subepidermal low-echogenic band thickness and improved density, and in vivo reflectance confocal microscopy indicated improved extracellular-matrix structure versus placebo. The MALDI-MSI work itself was applied to age-related changes, and the authors describe the study as preliminary.

Yang et al., Skin Res Technol, 2024;30(7):e13790 ran a 12-week clinical evaluation of an eye cream whose active complex included palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7 alongside a yeast/rice fermentation filtrate and N-acetylneuraminic acid, reporting gains in hydration (28.12%), elasticity (18.81%) and collagen density (54.99%). Three caveats travel with it: the measurements are against baseline rather than a vehicle-controlled arm, several authors are with the manufacturer’s R&D center, and a four-ingredient complex offers no way to attribute any of the result to this peptide specifically.

A 2021 review that screened 88 facial cosmetics for sensitive skin from 19 multinational brands found palmitoyl tetrapeptide-7 in exactly one product, and concluded that no studies could be found demonstrating its efficacy for regulating skin inflammation or wound healing, or for controlling sensitive-skin symptoms — only two patents describing such use. The same review noted that across the seven cosmetic peptides it examined, the available data sit mostly in patents and supplier brochures rather than randomized placebo-controlled studies (Resende et al., Pharmaceuticals (Basel), 2021;14(8):702).

The free tetrapeptide rigin has its own peer-reviewed literature from the immunology and structural-biology side: NMR and molecular-modeling work characterized an unusual type VII beta-turn conformation for the bioactive peptide in DMSO (Ashish et al., Eur J Biochem, 2000;267(5):1455-1463), a finding later reproduced in aqueous solution (Kumar & Kishore, J Pept Sci, 2010;16(9):456-464), and analog studies showed immunomodulatory activity in mice (Dutta et al., Int Immunopharmacol, 2001). None of this has progressed to human trials in any indication.

Common dosage forms

Palmitoyl tetrapeptide-7 is a topical-only compound in practice. It is sold in finished serums and creams — most often as part of a Matrixyl 3000-type blend, where the peptide actives are present at low parts-per-million concentrations — and by cosmetic-ingredient and research suppliers as water- or glycerin-based stock solutions and as raw lyophilized powder. The free, unpalmitoylated tetrapeptide (GQPR) is sold separately by peptide-synthesis suppliers as a laboratory reagent. It is not sold or studied as an injectable in the way metabolic or recovery peptides are.

Key considerations

• Regulatory status: Palmitoyl tetrapeptide-7 is a cosmetic ingredient, not an approved drug, and has never been through FDA drug review. The Cosmetic Ingredient Review Expert Panel assessed it in 2018 alongside tripeptide-1, hexapeptide-12 and their metal salts and fatty acyl derivatives, and concluded that these ingredients are safe in cosmetics in the present practices of use and concentration described in that assessment (Johnson et al., Int J Toxicol, 2018;37(3_suppl):90S-102S). That is a safety finding about topical use at cosmetic levels — it says nothing about efficacy, and nothing about any other route.
• Two rigins: The original rigin is the free IgG-derived immunopeptide GQPR from the 1981 literature; the cosmetic Rigin is Sederma’s trademark for the palmitoylated version. Immunology papers about “rigin” describe the free peptide’s phagocytosis and immune effects — they are not efficacy evidence for the topical cosmetic ingredient.
• The two lanes point opposite ways: the free peptide’s published claim to fame is stimulating immune activity (phagocytosis on par with tuftsin, enhanced cell-mediated and humoral responses in mice), while the cosmetic ingredient is marketed for damping an inflammatory signal by lowering IL-6. Both framings are used to sell the same sequence. Nothing published reconciles them, and neither one substitutes for the other as evidence.
• INCI renaming: The same molecule was formerly named palmitoyl tetrapeptide-3; older ingredient labels and some chemical suppliers still use that name for CAS 221227-05-0. Two further label traps: Matrixyl 3000 is the two-peptide blend, not a synonym for this ingredient; and “palmitoyl oligopeptide,” which appears on older Matrixyl 3000-era labels and in the Mondon study, is a retired INCI name that was split in 2013 into palmitoyl tripeptide-1 (Pal-GHK) and palmitoyl hexapeptide-12 (Pal-KTTKS).
• Evidence gap: The core IL-6-modulation claim has no independent single-ingredient human study behind it, and the published clinical work uses multi-ingredient formulations — one of them supplier-authored, the other manufacturer-authored and uncontrolled — that cannot isolate this peptide’s contribution.
• Delivery question: As with other palmitoylated cosmetic peptides, how much intact peptide crosses the stratum corneum from finished products dosed at parts-per-million levels remains an open question in the peer-reviewed literature.