Wiki · Profile

Larazotide

AT-1001 · Larazotide Acetate

Immune SystemPhase III

MW: 725.8g/mol
Formula: C32H55N9O10

Larazotide, also known as larazotide acetate, is an eight-amino-acid peptide classified as a zonulin antagonist, derived from the zonulin family of proteins that regulate intestinal tight junctions. Researchers primarily study it for its potential to restore intestinal barrier function and its implications in various autoimmune and inflammatory diseases, including celiac disease and arthritis. Key findings from recent studies suggest that larazotide effectively reduces intestinal permeability associated with dysbiosis and inflammation, thereby potentially preventing the onset of autoimmune conditions. Preclinical evidence indicates its role in enhancing tight junction integrity and modulating immune responses, demonstrating promise in both gastrointestinal and systemic inflammatory contexts. Currently, larazotide is undergoing phase III clinical trials to further evaluate its efficacy and safety in patients with celiac disease.

Chemical Profile

Chemical Structure

Formula	C32H55N9O10
Molecular Weight	725.8 g/mol
CAS Number	258818-34-7
PubChem CID	9810532

Half-Life

INIntranasal

Not applicable

POOral

Poor bioavailability

Larazotide is rapidly metabolized and has limited oral bioavailability due to degradation in the gastrointestinal tract.

Mechanism

Mechanism of Action

Larazotide acetate acts as a zonulin antagonist, primarily targeting the signaling pathways associated with tight junction regulation, specifically inhibiting myosin light chain kinase (MLCK) activity, which reduces phosphorylation of myosin light chain (p-MLC) and subsequently decreases tension on actin filaments. This modulation facilitates the closure of tight junctions, thereby restoring intestinal barrier integrity and reducing epithelial permeability. While the precise molecular interactions and additional signaling pathways involved in Larazotide's action are still being elucidated, its efficacy in enhancing barrier function in conditions like celiac disease and inflammatory bowel disease is well-supported.

Research

35 Research Publications

2,005

Total Citations

Human/RCT

5.9

Avg. Influence

2026

Latest

Sort

Filter

01Top

#01

Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis.

Tajik Narges, et al. · Nature communications · 2020

AnimalInfluence24.0

394

Researchers observed that treatment with the zonulin antagonist larazotide acetate effectively reduces arthritis onset by restoring intestinal barrier integrity in autoimmune mice.

Key findings

01Zonulin is highly expressed in autoimmune conditions and is linked to a leaky gut and inflammation.
02Restoring the intestinal barrier using certain compounds can inhibit the development of arthritis.
03A specific zonulin antagonist was effective in reducing the onset of arthritis by improving intestinal barrier function.

0.25, 1, 4, or 8 mgoral(human)14 days1 μMnot specified(pig)not specified1 mg totaloral(pig)not specified

PubMed

02Top

#02

Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.

HumanInfluence14.0

237

The study demonstrated that larazotide acetate at a 0.5 mg dose significantly reduced gastrointestinal symptoms in celiac disease patients adhering to a gluten-free diet.

0.25, 1, 4, or 8 mgoral(human)14 days1 μMnot specified(pig)not specified1 mg totaloral(pig)not specified

PubMed

03Top

#03

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier.

Case ReportInfluence12.0

208

Researchers observed that treatment with larazotide acetate in a child with MIS-C resulted in decreased plasma SARS-CoV-2 antigen levels and clinical improvement.

0.25, 1, 4, or 8 mgoral(human)14 days1 μMnot specified(pig)not specified1 mg totaloral(pig)not specified

PubMed

#04

Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study.

HumanInfluence8.0

195

The study demonstrated that larazotide acetate reduced gluten-induced immune reactivity and gastrointestinal symptoms in patients with celiac disease during a gluten challenge.

0.25, 1, 4, or 8 mgoral(human)14 days1 μMnot specified(pig)not specified1 mg totaloral(pig)not specified

PubMed

#05

A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge.

HumanInfluence12.0

179

The study demonstrated that larazotide acetate limited gluten-induced worsening of gastrointestinal symptom severity in celiac disease patients during a gluten challenge.

0.25, 1, 4, or 8 mgoral(human)14 days1 μMnot specified(pig)not specified1 mg totaloral(pig)not specified

PubMed

#06

Larazotide acetate regulates epithelial tight junctions in vitro and in vivo.

In VitroInfluence2.0

104

The study demonstrated that larazotide acetate inhibited the redistribution of tight junction proteins and preserved tight junction structure in intestinal epithelial cells exposed to gliadin fragments.

0.25, 1, 4, or 8 mgoral(human)14 days1 μMnot specified(pig)not specified1 mg totaloral(pig)not specified

PubMed

#07

The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate.

Khaleghi Shahryar, et al. · Therapeutic advances in gastroenterology · 2016

ReviewInfluence3.0

The review discussed larazotide acetate's ability to inhibit actin rearrangement caused by gliadin, highlighting its potential as a permeability regulator in celiac disease.

Key findings

01Researchers observed that gluten increases gut permeability in celiac disease, leading to various symptoms.
02The study highlighted larazotide acetate's ability to inhibit changes in gut cell structure caused by gluten.
03Clinical studies have been conducted to evaluate larazotide acetate as a potential therapy for managing celiac disease.

0.25, 1, 4, or 8 mgoral(human)14 days1 μMnot specified(pig)not specified1 mg totaloral(pig)not specified

PubMed

#08

Evolving Therapy for Celiac Disease.

ReviewInfluence5.0

The review discussed various emerging therapies for celiac disease, including zonulin antagonists like larazotide, aimed at improving patient management beyond a gluten-free diet.

0.25, 1, 4, or 8 mgoral(human)14 days1 μMnot specified(pig)not specified1 mg totaloral(pig)not specified

PubMed

#09

Larazotide acetate promotes tight junction assembly in epithelial cells.

In VitroInfluence1.0

The study demonstrated that larazotide acetate enhanced tight junction assembly and reduced paracellular permeability in epithelial cells, indicating its role as a tight junction modulator.

0.25, 1, 4, or 8 mgoral(human)14 days1 μMnot specified(pig)not specified1 mg totaloral(pig)not specified

PubMed

#10

Targeting endothelial tight junctions to predict and protect thoracic aortic aneurysm and dissection.

Yang Xueyuan, et al. · European heart journal · 2023

HumanInfluence4.0

Researchers studied the role of endothelial tight junctions in the development of thoracic aortic aneurysm and dissection (TAAD). They found that changes in these junctions could serve as early indicators of TAAD and that targeting these junctions may help reduce the incidence of this condition.

Key findings

01Researchers observed abnormal expressions of endothelial tight junctions in patients with TAAD.
02In a mouse model, early disruption of endothelial tight junction function was linked to the development of TAAD.
03The use of a specific inhibitor improved tight junction function and reduced the occurrence of TAAD in the mouse model.

PubMed

Safety

Safety & Handling

Research Gaps

There is a lack of comprehensive long-term human trials assessing the safety and efficacy of larazotide acetate across various inflammatory diseases beyond celiac disease. Additionally, the precise molecular mechanisms by which larazotide modulates tight junction dynamics and its effects on gut microbiota remain inadequately characterized, particularly in the context of chronic inflammatory conditions.

Solubility

Larazotide is soluble in water and has limited solubility in organic solvents such as DMSO.

Storage & Handling

Lyophilized

Stable for 2+ years at -20°C, 12 months at 4°C

Reconstituted

Use within 14 days when refrigerated at 4°C

Avoid

Avoid repeated freeze-thaw cycles, direct light

Solvent

Bacteriostatic water or sterile saline recommended

Safety information is derived from published research and may not reflect all known risks. This is not medical advice.

Legal Status

🇩🇪DE

Not approved as a medicinal product. Not a controlled substance. Sale as research chemical is a legal grey area.

🇺🇸US

Not approved by the FDA as a medicinal product. Not a controlled substance.

🇦🇺AU

Not approved by the TGA as a medicinal product.

🇬🇧UK

Not approved by the MHRA as a medicinal product.

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

Community Insights

Publications per Year

31 total

Mechanism

Tools

Reconstitution Calculator

Calculate reconstitution volumes for Larazotide

Serum Level Visualizer

Visualize Larazotide serum levels over time

Mechanism

Related Peptides

Angiotensin 1-7 Thymulin Thymosin Alpha-1 Alpha-MSH VIP Thymalin

Track Larazotide in PepStack

Log your research cycles, set reminders and visualize serum levels.

Download on theApp Store Get it onGoogle Play

Legal Disclaimer

This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer