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Tissue Repair · Reference monograph

Octapeptide regulator of intestinal tight junctions

Reference compound — not available from Purity Peptides. Shown for research context.

Overview

Larazotide acetate is a synthetic eight-amino-acid peptide (Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) developed as a regulator of epithelial tight junctions. Its sequence was derived from zonula occludens toxin (Zot), a protein produced by Vibrio cholerae, whose study by Alessio Fasano and colleagues led to the characterisation of zonulin, an endogenous modulator of intestinal permeability.

The peptide was taken into clinical development for coeliac disease, a condition in which gluten exposure is associated with increased paracellular permeability and immune activation. After a series of phase 2 studies, a phase 3 programme was undertaken, but it was discontinued in 2022 when an interim analysis indicated the study was unlikely to meet its primary endpoint. Larazotide is not approved by any major regulator. Its development history is frequently cited in discussions of how barrier-targeted agents should be evaluated. It remains a reference tool for researchers studying tight-junction dynamics, the zonulin pathway and gut barrier function in epithelial cell models and animal systems.

Mechanism studied

  1. Larazotide
  2. Intestinal epithelium
  3. Tight junctions
  4. Reduced permeability

Larazotide is thought to act locally on the intestinal epithelium rather than systemically. In cell models such as Caco-2 and IEC-6 monolayers, it reduces gliadin- and cytokine-induced redistribution of tight-junction proteins including ZO-1 and occludin, and limits rearrangement of the actin cytoskeleton. Proposed mechanisms include antagonism of zonulin-mediated signalling and inhibition of myosin light-chain kinase activity, which normally contracts the perijunctional actomyosin ring and opens the paracellular pathway. Functional readouts in these systems include transepithelial electrical resistance and flux of permeability markers. The precise molecular target has not been definitively established, which remains an important gap in the literature.

Research highlights

  • 01Derived from a fragment of Vibrio cholerae zonula occludens toxin, studied in the laboratory of Alessio Fasano.
  • 02Developed successively by Alba Therapeutics, Innovate Biopharmaceuticals and 9 Meters Biopharma under the codes AT-1001 and INN-202.
  • 03Phase 2 coeliac disease studies reported mixed results across endpoints, prompting a phase 3 study designed around symptom outcomes.
  • 04The phase 3 study was stopped in 2022 after an interim analysis; the compound has not been approved anywhere.
  • 05Open questions include the identity of its molecular target and whether barrier modulation alone can alter gluten-driven immune responses.

Latest published research

91 papers on PubMed →

  1. The impact of α3β4 partial agonist AT-1001 on oxycodone withdrawal

    Contreras KM et al. · Drug and alcohol dependence · 2026 Oct 8 · PMID 42914877

  2. New Framework for Multi-Electronic-State Dynamics and Its Validation for Photoisomerization of 1,3-Cyclohexadiene

    Shu Y et al. · Journal of chemical theory and computation · 2026 May 12 · PMID 42017512

  3. Potassium-Competitive Acid Blocker Increases Ileal Permeability and Exacerbates Ileal Inflammation under Stress Conditions in a Mouse Model of Eosinophilic Enteritis

    Yamamoto K et al. · Digestion · 2026 Apr 20 · PMID 42008374

  4. Birthweight and Academic Achievement Through Adolescence

    Wehby GL et al. · Academic pediatrics · 2026 Apr · PMID 41679541

  5. Coeliac disease and the intestinal barrier: mechanisms of disruption and strategies for restoration

    Damianos JA et al. · Gut · 2026 Mar 6 · PMID 40579122

  6. Integrated Role of Microbial, Fungal, and Plant-Derived Interventions in the Management of Celiac Disease: A Narrative Review

    Kubala K et al. · Cureus · 2026 Jan · PMID 41769533

  7. Preventive effects of Larazotide acetate (AT-1001) on non-alcoholic fatty liver diseases (NAFLD) in a mouse model

    Huang YC et al. · Pediatrics and neonatology · 2026 Jan · PMID 40562584

  8. Antibacterial hyaluronic acid hydrogel with sustained release of larazotide as effective colitis treatment

    Yu F et al. · Journal of controlled release : official journal of the Controlled Release Society · 2025 Nov 10 · PMID 40915363

Live feed from PubMed (NCBI) for “Larazotide Acetate”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.

Registered studies

29 on ClinicalTrials.gov →

From the public ClinicalTrials.gov registry for “Larazotide Acetate”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.

Key references

  1. [1]Leffler et al., 2015 — Gastroenterology
  2. [2]PubMed — reviews on larazotide and coeliac disease

FAQ

  • Zonulin is the name given to an endogenous protein later identified as pre-haptoglobin 2, proposed to increase intestinal permeability by disassembling tight junctions. Its discovery followed work on the cholera-derived toxin Zot, and larazotide was designed as a peptide that interferes with this pathway.

  • The sponsor reported in 2022 that an interim analysis indicated the study was unlikely to meet its primary endpoint, and the trial was discontinued. This outcome is frequently discussed as an example of the challenges of measuring symptom endpoints in coeliac disease research.

  • Researchers commonly use polarised intestinal epithelial monolayers such as Caco-2 cells, measuring transepithelial electrical resistance and tracer flux, as well as rodent and gluten-sensitive animal models. Tight-junction protein localisation by immunofluorescence is a common supporting readout.

FOR RESEARCH USE ONLY.Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.

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