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Metabolic & GLP-1 · Reference monograph

Uroguanylin-analogue peptide for chronic constipation

Reference compound — not available from Purity Peptides. Shown for research context.

Overview

Plecanatide is a 16-amino-acid peptide analogue of uroguanylin, an endogenous hormone produced in the intestine that regulates fluid and electrolyte balance. Its sequence is identical to human uroguanylin except for a single substitution of glutamic acid for aspartic acid at position 3, which was found to enhance binding to its receptor. It was developed by Synergy Pharmaceuticals under the code SP-304.

Plecanatide was approved by the FDA in 2017, marketed as Trulance, for chronic idiopathic constipation and later for irritable bowel syndrome with constipation. It is not approved in the EU. Its research interest lies in the pH sensitivity it inherits from uroguanylin: the native hormone is more active in the mildly acidic environment of the proximal small intestine, whereas guanylin is more active in the more alkaline distal gut. Plecanatide therefore offers a tool for studying how luminal pH shapes receptor activation along the length of the intestine, and it is frequently compared with linaclotide, which lacks this pH-dependent profile.

Mechanism studied

  1. Plecanatide
  2. GC-C receptor (pH-dependent)
  3. cGMP signalling
  4. Intestinal transit

Plecanatide binds guanylate cyclase-C on the apical surface of intestinal epithelial cells, generating cyclic GMP. Elevated cGMP activates protein kinase G II, which phosphorylates and opens the CFTR channel, increasing chloride and bicarbonate secretion into the lumen. Water follows by osmosis, softening luminal contents and accelerating transit in experimental models. Like uroguanylin, plecanatide adopts its most active conformation under mildly acidic conditions, so receptor activation is favoured in the proximal small intestine. Systemic absorption is minimal in pharmacokinetic studies, so its actions are largely confined to the gastrointestinal tract.

Research highlights

  • 01Modelled on uroguanylin, an intestinal hormone discovered in the early 1990s alongside guanylin.
  • 02A single residue substitution improves receptor binding while preserving uroguanylin's pH sensitivity.
  • 03Approved in the US in 2017, becoming the second guanylate cyclase-C agonist to reach the market.
  • 04Comparative research contrasts its pH-dependent activity with the pH-independent profile of linaclotide.
  • 05Open questions include the physiological significance of uroguanylin signalling beyond the gut, such as renal and satiety effects.

Latest published research

128 papers on PubMed →

  1. Constipation with bloating: a clinical approach to evaluation and management

    Cangemi DJ et al. · Annals of medicine · 2026 Dec · PMID 42319080

  2. Pharmacotherapy of Irritable Bowel Syndrome with Constipation in Children: An Update on Clinical Progress and Successes

    Puoti MG et al. · Drugs · 2026 Nov · PMID 42773320

  3. Gut relief revisited: plecanatide in chronic idiopathic constipation and irritable bowel syndrome with constipation - a systematic review and meta-analysis with GRADE assessment

    Aboelkhier MM et al. · BMC gastroenterology · 2026 Oct 26 · PMID 42934540

  4. Constipation-predominant irritable bowel syndrome treatment options Linaclotide, Lubiprostone, Plecanatide, and Tenapanor: analysis of the FDA Adverse Event Reporting System (FAERS) database

    Andrews MB et al. · Expert opinion on drug safety · 2026 Oct · PMID 40503810

  5. Patients' Real-World Experiences With Pharmacologic Therapies for Irritable Bowel Syndrome With Constipation: A Mixed-Methods Analysis and Classification of Social Media and E-Forum Posts

    Khalil C et al. · Neurogastroenterology and motility · 2026 Sep · PMID 42694017

  6. Irritable Bowel Syndrome with Constipation: Diagnosis and Multisymptom Management Beyond Abdominal Pain and Bowel Movement Frequency: A Review

    Shah ED et al. · Advances in therapy · 2026 Sep · PMID 42283961

  7. A targeted partial reduction cyanylation strategy coupled with HRMS for accurate disulfide bridge mapping in disulfide rich cyclic peptides

    Chaturvedi S et al. · Journal of chromatography. A · 2026 Aug 30 · PMID 42242129

  8. Post-marketing safety assessment of constipation drugs: a real-world pharmacovigilance study based on FAERS database

    Zhang W et al. · Expert opinion on drug safety · 2026 Jul · PMID 39950440

Live feed from PubMed (NCBI) for “Plecanatide”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.

Registered studies

15 on ClinicalTrials.gov →

From the public ClinicalTrials.gov registry for “Plecanatide”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.

Key references

  1. [1]Manufacturer's prescribing information — FDA / EMA / ANVISA
  2. [2]Miner et al., 2017 — Am J Gastroenterol

FAQ

  • Plecanatide is identical to human uroguanylin except for one substitution, glutamic acid in place of aspartic acid at position 3. This change was reported to improve binding to guanylate cyclase-C while retaining pH-sensitive activity.

  • Like uroguanylin, plecanatide is most active in mildly acidic conditions typical of the proximal small intestine. Researchers use this property to study how luminal pH influences receptor activation along the gut.

  • Plecanatide is approved by the FDA as a prescription medicine for chronic idiopathic constipation and IBS with constipation. It is not approved in the EU. Research material is intended for laboratory use only.

FOR RESEARCH USE ONLY.Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.

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