Larazotide
| Category | Compounds |
|---|---|
| Also known as | Larazotide Acetate, AT-1001, INN-202 |
| Last updated | 2026-04-14 |
| Reading time | 3 min read |
| Tags | gut-barriertight-junctionceliacintestinalresearch |
Overview
Larazotide (larazotide acetate, AT-1001) is a synthetic octapeptide developed as an inhibitor of zonulin-mediated increases in intestinal permeability. Zonulin, described by Alessio Fasano and colleagues, is a human analog of the bacterial zonula occludens toxin that reversibly disassembles intestinal tight junctions. By blocking zonulin signaling, larazotide is designed to preserve the gut barrier under conditions — such as gluten exposure in celiac disease — that otherwise trigger increased permeability.
Larazotide reached late-stage clinical trials for celiac disease as an adjunct to the gluten-free diet, aiming to reduce symptoms in patients who remain symptomatic despite dietary adherence. Although a phase 3 trial did not meet its primary endpoint, the program contributed substantially to understanding of tight-junction biology and remains a key reference in gut-barrier research.
In research catalogs, larazotide is grouped with gut-directed peptides such as BPC-157, KPV, GLP-2, Linaclotide, and Pentosan Polysulfate. Interest in "leaky gut" hypotheses in autoimmune, metabolic, and neurologic conditions keeps larazotide in continuing discussion.
Structure / Chemistry
Larazotide is a synthetic octapeptide with sequence Gly-Gly-Val-Leu-Val-Gln-Pro-Gly, administered as the acetate salt. It is engineered for oral activity in the intestinal lumen rather than for systemic absorption.
Mechanism of Action
Larazotide acts locally in the intestinal lumen to antagonize zonulin signaling. By preventing zonulin-induced disassembly of tight junctions, it preserves paracellular barrier function and reduces translocation of antigens such as gliadin peptides across the epithelium. Because it is not systemically absorbed, its effects are confined to the GI tract.
Research Summary
| Area | Finding | Reference |
|---|---|---|
| Celiac phase 2 | Reduced symptoms with persistent gluten exposure | Leffler et al., Gastroenterology 2015 |
| Celiac phase 3 | CeDLara study did not meet primary endpoint | Multiple sponsor disclosures |
| Mechanism | Zonulin pathway characterization | Fasano et al., Physiol Rev 2011 |
| Permeability | Reduced gliadin-induced permeability in models | Gopalakrishnan et al., Peptides 2012 |
| Tight junctions | Preservation of ZO-1 and occludin | Multiple preclinical studies |
Pharmacokinetics
Larazotide is designed to act locally in the intestinal lumen and has minimal systemic absorption. Clinical trials used oral dosing before meals. Specific doses referenced are trial parameters, not guidance.
Common Discussion Topics
- Relationship between zonulin biology and broader "leaky gut" hypotheses.
- Phase 3 outcomes and implications for the zonulin-targeting approach.
- Use of barrier-modulating peptides in autoimmune research.
- Comparison with BPC-157 and KPV for gut protection.
- Potential applications beyond celiac disease.
Related Compounds
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Related entries
- BPC-157— A 15-amino-acid peptide derived from human gastric juice protein BPC, extensively studied in animal models for its role in tissue repair, cytoprotection, and wound healing acceleration.
- GLP-2 (Glucagon-Like Peptide 2)— A 33-amino acid proglucagon-derived intestinal peptide released from L-cells after meals, acting through the GLP-2 receptor to promote intestinal mucosal growth, enhance nutrient absorption, and maintain gut barrier function — the basis for the short bowel syndrome treatment teduglutide.
- KPV— A naturally occurring anti-inflammatory tripeptide derived from the C-terminal end of alpha-melanocyte-stimulating hormone (alpha-MSH), studied for its effects on inflammatory signaling and gut mucosal integrity.
- Linaclotide— A synthetic 14-amino-acid peptide agonist of guanylate cyclase-C, linaclotide is an FDA-approved oral peptide used to treat irritable bowel syndrome with constipation and chronic idiopathic constipation by stimulating intestinal fluid secretion and reducing visceral pain signaling.
- Pentosan Polysulfate— A semi-synthetic sulfated polysaccharide derived from beechwood hemicellulose, FDA-approved for interstitial cystitis (Elmiron) and used internationally for osteoarthritis, with structural similarity to heparin and endogenous glycosaminoglycans.