The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases

Curr Med Chem. 2021;28(28):5788-5807. doi: 10.2174/0929867328666210104110053.


Background: The involvement of intercellular tight junctions and, in particular, the modulation of their competency by the zonulin pathway with a subsequent increase in epithelial and endothelial permeability, has been described in several chronic and acute inflammatory diseases. In this scenario, Larazotide, a zonulin antagonist, could be employed as a viable therapeutic strategy.

Objective: The present review aims to describe recent research and current observations about zonulin involvement in several diseases and the use of its inhibitor Larazotide for their treatment.

Methods: A systematic search was conducted on PubMed and Google Scholar, resulting in 209 publications obtained with the following search query: "Larazotide," "Larazotide acetate," "AT-1001," "FZI/0" and "INN-202." After careful examination, some publications were removed from consideration because they were either not in English or were not directly related to Larazotide.

Results: The obtained publications were subdivided according to Larazotide's mechanism of action and different diseases: celiac disease, type 1 diabetes, other autoimmune diseases, inflammatory bowel disease, Kawasaki disease, respiratory (infective and/or non-infective) diseases, and other.

Conclusion: A substantial role of zonulin in many chronic and acute inflammatory diseases has been demonstrated in both in vivo and in vitro, indicating the possible efficacy of a Larazotide treatment. Moreover, new possible molecular targets for this molecule have also been demonstrated.

Keywords: AT-1001; Celiac disease; Chronic Inflammatory Disease; Diabetes.; FZI/0; INN-202; Intestinal permeability; Larazotide; Zonulin.

Publication types

  • Review

MeSH terms

  • Haptoglobins
  • Humans
  • Intestinal Mucosa
  • Oligopeptides*
  • Permeability
  • Protein Precursors*
  • Tight Junctions


  • Haptoglobins
  • Oligopeptides
  • Protein Precursors
  • zonulin
  • larazotide acetate