Larazotide Acetate (AT-1001)

1 Identity

Synthetic octapeptide, all-L, entirely proteinogenic, supplied as the acetate salt. A conventionally developed investigational drug substance rather than a gray-channel research peptide. Two CAS numbers are in commercial circulation for what A buyer thinks is one product: 258818-34-7 for the free base and 881851-50-9 for the acetate salt.

Sequence

H-Gly-Gly-Val-Leu-Val-Gln-Pro-Gly-OH; one-letter GGVLVQPG, eight residues, supplied as the acetate salt.

Molecular formula

C32H55N9O10 (free base). Mono-acetate salt C34H59N9O12 — the article named in this catalog record.

Average mass

725.85 Da free base (C32H55N9O10); on IUPAC 2021 abridged conventional atomic weights the formula gives 725.845. Mono-acetate C34H59N9O12 = 785.90, of which 7.6 percent of the gross weight is acetate; supplier catalogs print 785.9 for this salt and the arithmetic matches to within 0.01 Da. Mono-trifluoroacetate C34H56F3N9O12 = 839.87, of which 13.6 percent is trifluoroacetate — so a trifluoroacetate lot shipped in a bottle labeled acetate delivers about 6.4 percent less peptide than the gross weight implies. C-terminal amide 724.86. Gln6-deamidated species 726.83.

Monoisotopic mass

725.40719 Da neutral free base (C32H55N9O10). [M+H]+ 726.41447; [M+2H]2+ 363.71087; [M-H]- 724.39991. Mono-acetate 785.42832 neutral. C-terminal amide 724.42317, i.e. 0.98 Da lighter than the free acid — the opposite direction from most amide/acid pairs in this catalog, because here the free acid is the intended article. Gln6-deamidated species 726.39120, i.e. +0.98 Da, which means the deamidation product and the amide impurity sit almost exactly one dalton either side of the target and are separated from it by the same increment.

Salt / variant note

Six articles, of which the salt split is the live commercial risk. (1) Free base, CAS 258818-34-7, C32H55N9O10, 725.85 average / 725.40719 monoisotopic. (2) Mono-acetate, CAS 881851-50-9, C34H59N9O12, 785.90 / 785.42832 — the article named in this record. Two CAS numbers for one perceived product is itself a purchasing hazard and is documented here so that a mismatch between order and certificate is recognized as a registry split rather than mistaken for a substitution, and so that a real substitution is not excused as one. (3) Mono-trifluoroacetate C34H56F3N9O12, 839.87 / 839.40005 — what a supplier ships when it purifies by preparative reversed-phase chromatography in trifluoroacetic acid and skips the salt exchange, in a bottle labeled acetate; the single commonest identity defect in this class. (4) C-terminal amide C32H56N10O9, 724.86 / 724.42317 — 0.98 Da lighter than the intended free acid. (5) Gln6-deamidated species C32H54N8O11, 726.83 / 726.39120 — +0.98 Da, this sequence's characteristic degradation product, and isobaric in magnitude with the amide difference in the opposite direction, so a method that separates by mass alone can confuse the two; they must be separated chromatographically. (6) D-amino-acid larazotide derivatives, a family claimed in published US patent application 20230218706, "Larazotide derivatives comprising D-amino acids" — chemically distinct molecules, some of them exactly isobaric with the parent.

2 Class & testing panel

Form

Single article

Testing panel

P1 — panel definition

3 Primary sources & evidence

The index reports the design and provenance of the literature, not a conclusion about effect.

Human randomized controlled trials, by identifier and study type. Leffler DA et al., Gastroenterology 148(7):1311-9.e6, 2015, PMID 25683116, DOI 10.1053/j.gastro.2015.02.008, NCT01396213: multicenter randomized controlled trial, Phase 2, n=342 (340 mITT). Kelly CP et al., Alimentary Pharmacology and Therapeutics, 2012, DOI 10.1111/apt.12147: randomized placebo-controlled trial under gluten challenge. Leffler DA et al., American Journal of Gastroenterology, 2012, DOI 10.1038/ajg.2012.211: randomized double-blind study. Kelly CP et al., Gastroenterology, 2009, DOI 10.1016/s0016-5085(09)62182-x: Phase 2b, reported as a conference abstract. Systematic reviews and meta-analyses of randomized trials: Hoilat GJ et al., 2022, DOI 10.1016/j.clinre.2021.101782; Moole H et al., 2016, DOI 10.14309/00000434-201610001-01079; Abu-Zaid A et al., 2020, medRxiv preprint DOI 10.1101/2020.09.06.20189324, not peer reviewed. Narrative reviews: Khaleghi S et al., 2015, DOI 10.1177/1756283x15616576; Armandi 2022. Preclinical: Enomoto 2021, porcine model, delayed-release formulation. No product is approved in any jurisdiction.

4 Storage & specification

Storage

White lyophilized powder, acetate salt, in a screw-cap amber borosilicate vial with a PTFE-lined closure, non-sterile with no sterility claim, stored at -20 degrees C plus or minus 5 degrees C, tightly closed and desiccated, protected from light, equilibrated to ambient temperature before opening. Moisture is the control that matters and the reason is specific rather than general: both governing degradation routes on this sequence — N-terminal cyclization to cyclo(Gly-Gly) with chain truncation, and Gln6 deamidation — are hydrolytic, so a desiccant sachet in the secondary pack and a Karl Fischer result at every retest point are part of the specification rather than good practice. Reconstituted solution aliquoted single-use and held at -80 degrees C.

Shelf life

Provisional 24 months from QA release at -20 degrees C plus or minus 5 degrees C, desiccated, pending the company's own stability data on the first three commercial lots under an ICH Q1A(R2)-style protocol: 12 months real time with pulls at 0, 3, 6, 9 and 12 months at the labeled condition, plus 6 months accelerated at 40 degrees C / 75 percent relative humidity. The stability method must separately report cyclo(Gly-Gly) and the Gln6-deamidated species at every pull rather than a total-impurities figure, because both are slow hydrolytic routes whose growth is exactly what a pooled number hides. Extension beyond 24 months only on 12 months of real-time data at the labeled condition from three commercial lots.