Larazotide Acetate

Larazotide Acetate, also known by its development code AT-1001 and INN designation INN-202, is a synthetic eight-amino-acid peptide (octapeptide) with the sequence Gly-Gly-Val-Leu-Val-Gln-Pro-Gly (GGVLVQPG). The base peptide has a molecular formula of C32H55N9O10 and a molecular weight of approximately 725.8 g/mol (CAS 258818-34-7); as the acetate salt form specifically covered on this page, it carries PubChem CID 44146842 and CAS number 881851-50-9.

At Verified Peptides, we classify Larazotide Acetate as a zonulin antagonist and tight junction modulator, studied primarily in the context of celiac disease and intestinal barrier permeability research. It was originally developed by Alba Therapeutics and later advanced by 9 Meters Biopharma, and it holds the distinction of being the only celiac disease drug candidate to have ever reached a Phase 3 clinical trial.

Unlike the injectable peptides elsewhere in this catalog, Larazotide Acetate is designed to act locally within the gastrointestinal tract rather than being absorbed systemically, and clinical research has administered it orally, consistent with its intended mechanism of action at the intestinal epithelial barrier itself rather than through systemic circulation.

This local, non-systemic design also means that Larazotide Acetate's research profile is evaluated somewhat differently than a systemically absorbed compound: pharmacokinetic research has generally found minimal detectable plasma concentrations following oral dosing, which researchers studying this compound have treated as consistent with (rather than contradicting) its intended local mechanism of action, since a compound designed to act at the gut wall itself would not be expected to reach meaningful systemic circulation to begin with.

At Verified Peptides, we consider Larazotide Acetate's clinical research history a genuinely instructive case study in both a real positive signal and a real developmental setback. The pivotal Phase 2 trial (Leffler DA, et al., Gastroenterology, 2015; PMID 25683116) was a multicenter, double-blind, placebo-controlled study of 342 adults with biopsy-confirmed celiac disease who remained symptomatic despite maintaining a gluten-free diet for at least 12 months. Three doses were tested — 0.5 mg, 1 mg, and 2 mg, each three times daily. Only the lowest dose, 0.5 mg, achieved statistical significance on the primary endpoint (a 26% decrease in symptomatic days, p=0.022); the two higher doses showed no advantage over placebo, an example of a non-monotonic (non-linearly-increasing) dose-response relationship that is worth noting honestly rather than glossing over, since it complicates any simple "more is better" assumption about dosing in this compound's research history.

An earlier randomized, double-blind gluten-challenge study (PMID 22825365) had previously found that larazotide acetate reduced gluten-induced symptoms and blunted the rise in anti-tissue transglutaminase antibodies that typically follows a deliberate gluten challenge in celiac patients, providing supportive mechanistic evidence ahead of the larger Phase 2 trial.

Based on this positive Phase 2 signal, Larazotide Acetate advanced to a Phase 3 trial (CeDLara, ClinicalTrials.gov identifier NCT03569007) — the first and, to date, only celiac disease drug candidate ever to reach this stage of development. The 24-week trial enrolled 525 patients across three arms (0.25 mg, 0.5 mg, and placebo), with a primary endpoint measuring change in celiac disease symptom severity. In June 2022, the trial was discontinued following an interim analysis, which found that the sample size required to demonstrate a statistically significant treatment effect between the drug and placebo groups would be too large to be practically supportable — a stop for statistical futility rather than a safety failure or an outright negative result. We are noting this distinction carefully: a futility-driven discontinuation is a meaningfully different outcome from a trial that showed the drug does not work, even though neither resulted in an approved product.

As of this writing, Larazotide Acetate has not been approved by the FDA or any other regulatory agency for any indication, and no active Phase 3 or later-stage trial is registered following CeDLara's discontinuation. Research-grade Larazotide Acetate sold here is intended exclusively for laboratory research, not for human or animal use.

Larazotide Acetate holds a genuinely unique distinction in celiac disease drug development: it is the only compound targeting this condition to have ever reached a Phase 3 clinical trial, despite celiac disease affecting a well-characterized patient population with a clear unmet need beyond dietary management alone. Its Phase 3 discontinuation for statistical futility, rather than for a safety issue or a clearly negative efficacy result, is a distinct outcome from many other discontinued development programs, and researchers evaluating its evidence base should weigh the positive Phase 2 signal on its own merits rather than assuming the Phase 3 stoppage disproves it.

The zonulin pathway that Larazotide Acetate targets has research implications well beyond celiac disease specifically. Zonulin signaling and intestinal permeability have been studied in connection with several other autoimmune and inflammatory conditions, including type 1 diabetes, inflammatory bowel disease, and some neurological and metabolic research contexts, based on the broader hypothesis — still actively debated in the research literature — that increased intestinal permeability may play a contributing role in a wider range of immune-related conditions beyond celiac disease alone.

Larazotide Acetate's oral, locally acting, minimally systemically absorbed design is a deliberate pharmaceutical strategy distinct from most peptide drug candidates, which typically require injection specifically because oral peptides are usually degraded by digestive enzymes before they can act. Because Larazotide Acetate's intended site of action is the gut epithelium itself, avoiding systemic absorption is treated as a feature of its design rather than a limitation, in contrast to peptides where oral bioavailability is instead a hard-won pharmaceutical achievement.

Ischemic intestinal injury research has separately explored Larazotide Acetate's tight-junction-supporting effects in animal models, including a study examining recovery of ischemia-injured porcine jejunal tissue, suggesting research interest in this compound's mechanism extends to gut barrier recovery contexts beyond celiac disease specifically.

At Verified Peptides, we require independent third-party HPLC purity testing and mass spectrometry identity confirmation for every batch of research-grade Larazotide Acetate we offer, and we make the Certificate of Analysis (COA) available for each lot. As an eight-amino-acid synthetic peptide sold in its acetate salt form, verifying both amino acid sequence integrity and salt-form consistency are relevant quality parameters for reproducible research use.

We source exclusively from manufacturers operating under Good Manufacturing Practice (GMP)-aligned quality systems, and every lot is independently verified rather than relying on a supplier's own internal testing alone. Researchers should always request and review the specific COA for their lot, checking purity percentage and confirmed molecular identity before use in any experimental protocol.

Because Larazotide Acetate's research applications typically involve gut-barrier and epithelial-permeability models, where the compound's activity is studied at a local tissue level rather than through systemic distribution, purity and identity verification remain just as important as for any systemically administered peptide, since an impure or misidentified sample can just as easily confound a local-tissue research model as a systemic one.

Lyophilized (freeze-dried) Larazotide Acetate is stable when stored at -20°C, protected from light and moisture, and can generally be expected to maintain integrity for extended periods in this unreconstituted form.

Once reconstituted with an appropriate sterile diluent, Larazotide Acetate solution should be stored refrigerated at 2–8°C and used within the documented timeframe for that lot, since reconstituted peptide solutions are generally more prone to degradation than the lyophilized form. Repeated freeze-thaw cycling should be avoided, and aliquoting into single-use portions where practical helps minimize unnecessary freeze-thaw exposure.

As with other research peptides, prolonged exposure to heat, direct light, or extended room-temperature storage will accelerate degradation and compromise structural integrity relevant to research applications. Following the lot-specific storage documentation provided with each order remains the most reliable way to preserve sample validity for experimental work.