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A uroguanylin copy that works in the gut lumen and barely enters the blood — an oral peptide by design.
Also known as: Trulance · Guanilib · SP-304
Part of the Metabolic & GLP-1 peptides cluster
Overview
Plecanatide (Trulance) is a synthetic 16-residue analogue of human uroguanylin (NDECELCVNVACTGCL, two disulfides) that activates guanylate cyclase-C in the gut, raising cGMP and driving chloride and water into the lumen. It was FDA-approved for chronic idiopathic constipation in January 2017 and for IBS with constipation in January 2018, is minimally absorbed, and carries a strong guideline recommendation for chronic constipation.
Source & context
Biological / chemical source: Synthetic 16-amino-acid uroguanylin analog
Primary research or clinical context: Approved (FDA, January 2017) for chronic idiopathic constipation in adults and (January 2018) for irritable bowel syndrome with constipation
What plecanatide is
Plecanatide is an oral guanylate cyclase-C agonist developed by Synergy Pharmaceuticals: a synthetic analogue of human uroguanylin, the 16-amino-acid peptide that regulates ion and fluid transport in the gastrointestinal tract (Al-Salama and Syed, Drugs 2017). Its sequence, NDECELCVNVACTGCL, is held in shape by two disulfide bonds between Cys4–Cys12 and Cys7–Cys15 (IUPHAR ligand 9069). It received its first global approval in the United States in January 2017 for chronic idiopathic constipation in adults, and the FDA expanded the approval to irritable bowel syndrome with constipation in January 2018. It is marketed as Trulance.
Mechanism: cGMP in the gut lumen
Agonist activation of GC-C receptors on the intestinal epithelium stimulates intracellular production of cyclic GMP. That activates the cystic fibrosis transmembrane conductance regulator (CFTR), the apical channel that pumps chloride out of enterocytes; water follows into the lumen, softening stool and improving transit (IUPHAR record). Uroguanylin, the parent hormone, is most active in the slightly acidic environment of the upper small intestine, and plecanatide is designed to keep that pH-dependent behaviour — the mechanistic point of difference from linaclotide, which mimics the related hormone guanylin. Because the target is luminal, the drug does not need to be absorbed.
Clinical evidence
The phase 3 programme in chronic idiopathic constipation and IBS-C supported the approvals (Al-Salama and Syed, 2017; Rao, Therapeutic Advances in Gastroenterology 2018). A more recent phase 3 trial in 648 Chinese patients with functional constipation randomised 1:1 to plecanatide 3 mg or placebo for 12 weeks found durable overall complete spontaneous bowel movement (CSBM) response in 23.5% versus 10.2%, mean weekly CSBMs of 1.89 versus 0.9 and spontaneous bowel movements of 2.33 versus 1.03, with all secondary endpoints favouring plecanatide; the most common treatment-related adverse event was diarrhoea, in 4.3% versus 0.6% (Bai et al., Drugs 2025). A network meta-analysis of 33 randomised trials with 17,214 patients compared the constipation drugs in the absence of head-to-head trials (Luthra et al., Lancet Gastroenterology and Hepatology 2019).
| Endpoint | Plecanatide 3 mg | Placebo |
|---|---|---|
| Durable overall CSBM response | 23.5% | 10.2% |
| Mean weekly CSBMs | 1.89 | 0.9 |
| Mean weekly SBMs | 2.33 | 1.03 |
| Diarrhoea (treatment-related) | 4.3% | 0.6% |
Guideline position
The joint American Gastroenterological Association and American College of Gastroenterology guideline on chronic idiopathic constipation makes strong recommendations for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide and prucalopride in adults (Chang et al., Gastroenterology and American Journal of Gastroenterology 2023). For IBS-C, the AGA guideline gives linaclotide a strong recommendation with high certainty and plecanatide a conditional recommendation with moderate certainty, alongside tenapanor, tegaserod and lubiprostone (Chang et al., Gastroenterology 2022). That difference in certainty, rather than any head-to-head result, is the honest way to read “plecanatide versus linaclotide.”
Pharmacokinetics and safety
Plecanatide is minimally absorbed from the gastrointestinal tract; the drug and its active metabolite are not measurable in breast milk after recommended doses (LactMed, 2025), and it is described as a minimally absorbed GC-C agonist in the liver-injury database, where no hepatotoxicity signal is recorded (LiverTox, 2019). Diarrhoea is the characteristic adverse effect, as expected from the mechanism. Trials in children aged 6 to under 18 with IBS-C and functional constipation are registered.
Regulatory status as of September 2026
Plecanatide is an approved prescription medicine in the United States for chronic idiopathic constipation and IBS-C. The 2025 Chinese phase 3 trial supports registration there. It is not a grey-market product; it is a pharmacy peptide taken by mouth, which makes it a useful counter-example to the assumption that peptides cannot be oral drugs — they can, when the target is in the gut.
Plecanatide vs linaclotide and the guanylin family
Linaclotide and plecanatide are both GC-C agonists; linaclotide mimics guanylin and plecanatide mimics uroguanylin, with its pH-sensitive profile. Guidelines rate linaclotide's IBS-C evidence more certain, and both strongly for chronic constipation (Chang et al., 2022, 2023). Neither is absorbed to a meaningful extent, and both cause diarrhoea by the same mechanism. The uroguanylin and guanylin hormones themselves, and the bacterial heat-stable enterotoxin that hijacks the same receptor to cause travellers' diarrhoea, are the biological background.
Sequence
One-letter sequence commonly cited for Plecanatide (educational; isoforms and modifications may differ):
NDECELCVNVACTGCL
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- 16 residues NDECELCVNVACTGCL; analogue of human uroguanylin
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C65H104N18O26S4
- Average reference mass
- ≈ 1,681.9
- Plasma half-life
- Not meaningful systemically: minimally absorbed; drug and active metabolite are not measurable in breast milk (LactMed)
- Receptors
- Guanylate cyclase-C (GC-C) on the luminal surface of intestinal epithelium → intracellular cGMP → CFTR activation → chloride and water efflux into the lumen
- Backbone
- 16 residues NDECELCVNVACTGCL; analogue of human uroguanylin
- Status
- Approved (FDA): chronic idiopathic constipation, January 2017; IBS-C, January 2018 (IUPHAR record; Al-Salama & Syed, 2017)
Two disulfide bonds, Cys4–Cys12 and Cys7–Cys15, stabilise the fold against digestion (IUPHAR record)
- PubChem CID: 70693500
- IUPHAR ligand: 9069
- ChEMBL: CHEMBL2103867
- CAS RN: 467426-54-6
- UNII: 7IK8Z952OK
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 15 registered studies with “Plecanatide” as an intervention (snapshot 2026-09-06). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07723924 | This is a Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study of the Efficacy and | Phase 2 | active not recruiting | 2026-07-23 |
| NCT05107219 | GCC Agonist Signal in the Small Intestine | Phase 1 | completed | 2026-04-07 |
| NCT03596905 | Efficacy and Safety of Plecanatide in Children 6 to <18 Years With Irritable Bowel Syndrome With Constipation | Phase 2 | completed | 2025-12-31 |
| NCT05151328 | Efficacy and Safety of Plecanatide Comparing With Placebo in the Treatment of Functional Constipation | Phase 3 | completed | 2024-07-11 |
| NCT02706483 | Long Term Safety Study of Plecanatide | Phase 3 | completed | 2020-08-18 |
| NCT01053962 | SP-304 Dose Ranging Study in Patients With Chronic Idiopathic Constipation | Phase 2 | completed | 2020-01-02 |
Plecanatide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: 16 residues NDECELCVNVACTGCL; analogue of human uroguanylinAverage reference mass: 1,681.9 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Plecanatide
What is Plecanatide?+
Plecanatide (Trulance) is a synthetic 16-residue analogue of human uroguanylin (NDECELCVNVACTGCL, two disulfides) that activates guanylate cyclase-C in the gut, raising cGMP and driving chloride and water into the lumen. It was FDA-approved for chronic idiopathic constipation in January 2017 and for IBS with constipation in January 2018, is minimally absorbed, and carries a strong guideline recommendation for chronic constipation.
What Canadian product status is recorded for Plecanatide?+
Canadian product status for Plecanatide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Plecanatide?+
Plecanatide is commonly described as approximately 16 amino acids (Guanylate cyclase-C agonist).
What is plecanatide?+
An oral 16-residue analogue of the gut hormone uroguanylin that activates guanylate cyclase-C, raising cGMP and drawing water into the intestine. It is approved as Trulance for chronic idiopathic constipation and IBS-C.
How does plecanatide work?+
It binds GC-C on the intestinal lining, increasing cGMP, which activates the CFTR chloride channel; water follows chloride into the lumen and softens stool.
Is plecanatide absorbed?+
Minimally. The drug and its metabolite are not measurable in breast milk after recommended doses, and it acts from the gut lumen.
Plecanatide vs linaclotide?+
Both are GC-C agonists. Guidelines recommend both strongly for chronic idiopathic constipation; for IBS-C, linaclotide's recommendation is strong and plecanatide's conditional (Chang et al., 2022, 2023).
What are plecanatide's side effects?+
Diarrhoea is the characteristic one — 4.3% versus 0.6% on placebo in the 2025 phase 3 trial (Bai et al., 2025).
When was plecanatide approved?+
January 2017 for chronic idiopathic constipation and January 2018 for IBS-C, by the FDA.
Further reading
- PK conceptsWhy Peptides Have Short Half-Lives (And How Engineers Fix It)Proteases, renal clearance, DPP-4, PEGylation, lipidation, cyclization—educational guide to peptide pharmacokinetics concepts.
- FoundationsGLP-1 vs GIP vs Glucagon: Incretin Receptor Classes ExplainedAn educational overview of the incretin and metabolic receptor classes—GLP-1, GIP, and glucagon—and how single, dual, and triple receptor agonism differ mechanistically.
- ManufacturingPeptide Synthesis Basics for Non-ChemistsPlain-language introduction to solid-phase peptide synthesis (SPPS), purification, and why custom peptides cost what they cost.
Related peptides
References & further reading
- 1.Al-Salama et al. (2017). Plecanatide: First Global Approval. Drugs
- 2.Bai et al. (2025). Efficacy and Safety of Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Drugs
- 3.Brenner et al. (2025). The Effectiveness of Plecanatide for Treating Constipation and Bloating in Patients Aged 18 to 40 Years With Irritable Bowel Syndrome: Utilization of a New Composite Trisymptom Endpoint. J Gastroenterol Hepatol
- 4.Boulete et al. (2018). Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models. World J Gastroenterol
- 5.Fan et al. (2025). A pharmacovigilance study of the association between linaclotide/plecanatide and muscle spasms based on food and drug administration adverse event reporting system. Front Pharmacol
- 6.Rao et al. (2023). Influence of Demographic Factors on Clinical Outcomes in Adults With Chronic Idiopathic Constipation Treated With Plecanatide. Clin Transl Gastroenterol
- 7.Kamuda et al. (2018). Plecanatide (Trulance) for Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation. P T
- 8.Bassotti et al. (2019). Plecanatide for the treatment of chronic idiopathic constipation in adult patients. Expert Rev Clin Pharmacol
- 9.Chang et al. (2023). AGA–ACG clinical practice guideline: pharmacological management of chronic idiopathic constipation. Gastroenterology
- 10.Chang et al. (2022). AGA clinical practice guideline on the pharmacological management of irritable bowel syndrome with constipation. Gastroenterology
- 11.Luthra et al. (2019). Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis. Lancet Gastroenterology and Hepatology
- 12.Rao (2018). Plecanatide: a new guanylate cyclase agonist for the treatment of chronic idiopathic constipation. Therapeutic Advances in Gastroenterology
- 13.Drugs and Lactation Database (LactMed) (2025). Plecanatide
- 14.PubChem — Plecanatide, CID 70693500