Overview
Larazotide is a synthetic eight-amino-acid peptide that acts on the 'gaps' between the cells of the intestinal wall — the tight junctions. These connections determine how permeable the gut is.
In celiac disease and related conditions, those gaps stand open too far, letting substances such as gluten fragments cross the intestinal wall and trigger an immune reaction. Larazotide is designed to keep those connections tighter and thereby reduce permeability. It acts locally in the gut and is not absorbed systemically.
At Peptalis, larazotide is available strictly for research use only — in-vitro, not for human or animal use.
Mechanism of action
Larazotide regulates the tight junctions in the intestinal wall (as a zonulin antagonist) and thereby reduces intestinal permeability; it acts locally in the gut lumen.
Tight-junction regulation
- The tight junctions between gut cells regulate permeability; the protein zonulin opens those connections. Larazotide acts as a zonulin antagonist and keeps the connections tighter.
- In preclinical work, larazotide restored tight junctions and reduced permeability after injury (Slifer 2021).
Local action
- Larazotide is not absorbed systemically but acts in the gut lumen, which shapes its profile.
- It has been studied as an adjunct to a gluten-free diet in celiac disease, to reduce residual symptoms (Leffler 2015).
Research findings
- Human (phase 2b, RCT): larazotide reduces residual symptoms in celiac disease despite a gluten-free diet (Leffler 2015)
- Human (phase 2, RCT): larazotide during gluten challenge (Leffler 2012)
- Mechanism (animal): restoration of tight junctions after ischemic intestinal injury (Slifer 2021)
- Meta-analysis of RCTs in celiac disease (Hoilat 2021); phase 2a RCT in MIS-C in children (Yonker 2025)
Mechanism & preclinical
- Larazotide regulates the tight junctions as a zonulin antagonist; in an animal model it restored the connections after ischemic injury (Slifer 2021).
Human studies
- In a phase 2 study, larazotide dampened celiac activation during a gluten challenge (Leffler 2012).
- In a phase 2b RCT, the 0.5 mg dose reduced residual symptoms in celiac disease despite a gluten-free diet (Leffler 2015).
- A systematic review/meta-analysis summarized the RCTs (Hoilat 2021); more recently, a phase 2a RCT studied larazotide in children with post-COVID MIS-C (Yonker 2025).
Research context
This profile describes what has been done and found in research. Regulatory and clinical facts are facts about the respective trials and authorities, not claims about a Peptalis product; the compound is for in-vitro laboratory research only (RUO).
Open questions
- The celiac phase 3 trial was terminated early for futility; there is no approved indication.
- Most evidence concerns phase 2/2b; large, completed phase 3 confirmation is lacking.
- The role of zonulin/tight-junction regulation in broader conditions is still being worked out.
Research outlook
Larazotide is a well-characterized model system for tight-junction regulation and gut-barrier research.
It broadens the immune domain with the gut-barrier axis, alongside the thymic and antimicrobial peptides.
Scientific interest
A unique mechanism: local tight-junction regulation / zonulin antagonism in the gut.
Multiple published human RCTs in celiac disease.
Broadens the immune domain to the gut barrier.
Specifications
| Sequence | Gly-Gly-Val-Leu-Val-Gln-Pro-Gly (GGVLVQPG) — synthetisch octapeptide |
|---|---|
| Molecular formula | C₃₂H₅₅N₉O₁₀ |
| Molecular weight | 725.8 Da |
| CAS | 258818-34-7 · PubChem CID 9810532 |
| Research phase | Emerging human research |
References
- A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge · Leffler DA, et al. · Am J Gastroenterol · 2012
- Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial · Leffler DA, et al. · Gastroenterology · 2015
- Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions · Slifer ZM, et al. · PLoS One · 2021
- Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials · Hoilat GJ, et al. · Clin Res Hepatol Gastroenterol · 2021
- Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide · Yonker LM, et al. · Sci Transl Med · 2025
Availability
Not in catalogue · Profile complete · verification and sourcing not yet finished