ArticleJournal of medicinal chemistry2021
Improving the Gastrointestinal Stability of Linaclotide.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Combined linaclotide and polyethylene glycol electrolyte for colonoscopy preparation: a network meta-analysis of 14 randomized controlled trials.International journal of colorectal disease · 2025Pooled it
- Strategies for overcoming multiple barriers of oral administration of protein and peptide therapeutics.Materials today. Bio · 2026Review
- Synthesis of Cyclic Hexapeptides via the Hydrazide Method and Evaluation of Their Antibacterial Activities.Molecules (Basel, Switzerland) · 2025Article
- Article
- Intestinal biofilms: pathophysiological relevance, host defense, and therapeutic opportunities.Clinical microbiology reviews · 2024Review
- Article
- DRA involvement in linaclotide-stimulated bicarbonate secretion during loss of CFTR function.JCI insight · 2024Article
- Key role of down-regulated in adenoma (bioRxiv : the preprint server for biology · 2024Article
- Engineering Enhanced Antimicrobial Properties in α-Conotoxin RgIA through D-Type Amino Acid Substitution and Incorporation of Lysine and Leucine Residues.Molecules (Basel, Switzerland) · 2024Article
- Bowel preparation efficacy and discomfort of 2 L polyethylene glycol combined with linaclotide versus 3 L polyethylene glycol: a noninferiority, prospective, multicenter, randomized controlled trial.Therapeutic advances in gastroenterology · 2024Article
- Bowel preparation efficacy and safety of compound polyethylene glycol electrolyte powder combined with linaclotide for colonoscopy: A randomized controlled trial.JGH open : an open access journal of gastroenterology and hepatology · 2023Article
- Localised Delivery of Macromolecules to the Large Intestine: Translation to Clinical Trials.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Article
- On the Utility of Chemical Strategies to Improve Peptide Gut Stability.Journal of medicinal chemistry · 2022Article
- Posttranslational modifications of α-conotoxins: sulfotyrosine and C-terminal amidation stabilise structures and increase acetylcholine receptor binding.RSC medicinal chemistry · 2021Article
- Chemical Synthesis of TFF3 Reveals Novel Mechanistic Insights and a Gut-Stable Metabolite.Journal of medicinal chemistry · 2021Article
- Challenges and opportunities in delivering oral peptides and proteins.Expert opinion on drug deliveryReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High susceptibility to proteolytic degradation in the gastrointestinal tract limits the therapeutic application of peptide drugs in gastrointestinal disorders. Linaclotide is an orally administered peptide drug for the treatment of irritable bowel syndrome with constipation (IBS-C) and abdominal pain. Linaclotide is however degraded in the intestinal environment within 1 h, and improvements in gastrointestinal stability might enhance its therapeutic application. We therefore designed and synthesized a series of linaclotide analogues employing a variety of strategic modifications and evaluated their gastrointestinal stability and pharmacological activity at its target receptor guanylate cyclase-C. All analogues had substantial improvements in gastrointestinal half-lives (>8 h vs linaclotide 48 min), and most remained active at low nanomolar concentrations. This work highlights strategic approaches for the development of gut-stable peptides toward the next generation of orally administered peptide drugs for the treatment of gastrointestinal disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.