Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
Larazotide Acetate (formerly AT-1001, then INN-202) is a synthetic octapeptide that inhibits the zonulin-mediated opening of intestinal tight junctions. It is formulated as an oral capsule, not an injectable. Unlike most peptides in this library, larazotide is designed to act locally in the gut lumen — it is not meant to be systemically absorbed.
History
The zonulin pathway was characterized by Alessio Fasano's group at the University of Maryland in the 2000s. Fasano demonstrated that zonulin — a homolog of zonula occludens toxin from Vibrio cholerae — reversibly opens intestinal tight junctions, and that elevated zonulin activity is implicated in celiac disease and other autoimmune conditions. Larazotide was developed as a peptide antagonist of this pathway.
Alba Therapeutics took the compound through Phase II, demonstrating reduced celiac symptoms in patients on a gluten-free diet who still experienced exposure-related symptoms. The asset moved to Innovate Biopharmaceuticals and then to 9 Meters Biopharma, which initiated the Phase III CeDLara trial — the largest celiac drug trial ever conducted at that point. In June 2022, 9 Meters announced that CeDLara had failed to meet its primary endpoint and discontinued development.
Regulatory status
Larazotide is investigational. It has not been approved by the FDA, EMA, or any other major regulator. The Phase III failure and program discontinuation in 2022 ended the most advanced commercial development path. Research peptide and compounding sources continue to make it available for non-approved use.
Mechanism
The published mechanism papers describe larazotide as a zonulin pathway antagonist:
- Tight junction stabilization. Larazotide prevents zonulin-induced rearrangement of the tight junction proteins ZO-1 and occludin.
- Lumen-acting. The peptide remains in the gut lumen and acts on the apical side of the intestinal epithelium; it is not appreciably absorbed.
- Specificity. Activity has been demonstrated against zonulin and zonula occludens toxin; no off-target receptor binding has been characterized at therapeutic concentrations.
Half-life and dosing intervals
Because larazotide acts locally in the gut lumen and is not systemically absorbed, the relevant pharmacokinetic parameter is gut transit time rather than plasma half-life. Doses used in Phase II and Phase III trials were 0.5 mg or 1.0 mg, taken orally three times daily with meals (so the peptide is in the lumen when gluten exposure occurs).
Reconstitution example
Larazotide is an oral capsule, not an injectable. There is no reconstitution to perform. Research peptide suppliers typically offer it in 0.5 mg, 1 mg, or 2 mg capsule formats; the powder form would require encapsulation to be used as designed.
What to know
- Phase III failed. The most advanced clinical evaluation did not meet its primary endpoint. Reasons for failure remain under analysis but include possible underlying differences in gluten exposure between trial sites.
- Designed for celiac disease specifically. The zonulin pathway is implicated in other autoimmune conditions, but no controlled trial has validated larazotide outside celiac.
- Oral, not injectable. Unlike most peptides in this library, larazotide is taken orally and would lose activity if given by injection.
- Storage. Capsule formulations are stable at room temperature for the manufacturer-stated shelf life; the lyophilized powder requires refrigeration.
Sources
- 1.Leffler DA et al. (2015). Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet. Gastroenterology.
- 2.Fasano A (2012). Zonulin, regulation of tight junctions, and autoimmune diseases. Annals of the New York Academy of Sciences.
- 3.9 Meters Biopharma press release: discontinuation of CeDLara Phase III (June 2022).
- 4.Khaleghi S et al. (2016). The potential utility of tight junction regulation in celiac disease. Therapeutic Advances in Gastroenterology.