Name | Larazotide |
CAS number | 258818-34-7 |
Synonym | Unii-zn3R5560zv; larazotide; Glycylglycyl-L-valyl-L-leucyl-L-valyl-L-glutaminyl-L-prolylglycine; Gly-Gly-Val-Leu-Val-Gln-Pro-Gly; Glycine,glycylglycyl-L-valyl-L-leucyl-L-valyl-L-glutaminyl-L-prolyl-; AT2347; AT2347; AT-2347 |
Description | Larazotide is a synthetic eight–amino acid peptide that functions as a regulator of tight junctions in the intestinal epithelium, primarily developed as an adjunct therapy for celiac disease. It works by restoring and maintaining the integrity of the intestinal barrier, which is compromised in conditions like celiac disease where increased intestinal permeability (“leaky gut”) allows gluten-derived peptides to trigger immune responses. |
Structure |  |
Molecular Formula | C32H55N9O10 |
Molecular Weight | 725.83 g/mol |
Appearance | Solid powder |
Quality Standard | Enterprise Standard |
Assay | 99% |
Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
Storage Condition | Dry, dark and at 0 - 4 ℃ for short term (days to weeks) or -20 ℃ for long term (months to years). |
Shelf Life | >2 years if stored properly |
Sample package | Aluminium foil bag |
Commercial package | Aluminium Tin, Fiber drum |
Origin | China |
Larazotide is a synthetic eight–amino acid peptide that functions as a regulator of tight junctions in the intestinal epithelium, primarily developed as an adjunct therapy for celiac disease. It works by restoring and maintaining the integrity of the intestinal barrier, which is compromised in conditions like celiac disease where increased intestinal permeability (“leaky gut”) allows gluten-derived peptides to trigger immune responses.
Mechanism of Action
Larazotide acetate acts as an inhibitor of paracellular permeability by blocking the zonulin pathway, which normally increases intestinal permeability. In celiac disease, gliadin fragments bind to the CXCR3 receptor on intestinal epithelial cells, triggering a cascade that leads to the release of zonulin. Zonulin binds to receptors such as the epidermal growth factor receptor (EGFR) and protease-activated receptor 2 (PAR2), initiating signaling that causes tight junction disassembly and increased intestinal permeability.
Larazotide intervenes by competitively inhibiting zonulin from binding to its receptors, preventing tight junction disassembly and thus reducing paracellular permeability. This action helps maintain the normally closed state of tight junctions, limiting the passage of harmful substances through the intestinal barrier.
Additionally, larazotide has been shown to:
Promote redistribution and rearrangement of tight junction proteins (e.g., zonula occludens-1) and actin filaments to restore barrier function.
Inhibit myosin light chain kinase, reducing tension on actin filaments and facilitating tight junction closure.
Origin and Structure
Larazotide acetate is derived from a segment of the zonula occludens toxin (Zot) produced by Vibrio cholerae, which modulates intestinal permeability. The eight amino acid sequence (Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) responsible for this activity is shared with human zonulin, an endogenous regulator of tight junctions.
Clinical Development and Applications
Larazotide is currently in phase III clinical trials as an oral adjunct therapy for adults with celiac disease to reduce gluten-induced intestinal barrier dysfunction and associated symptoms.
Clinical studies have shown that larazotide is generally well tolerated, with no serious adverse events, and may reduce gastrointestinal symptom severity triggered by gluten exposure.
Beyond celiac disease, animal studies suggest potential benefits in other conditions involving barrier dysfunction, such as collagen-induced arthritis and intestinal ischemic injury.
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