Plecanatide is a 16-amino-acid synthetic peptide (MW ~1681.9 g/mol) that is a structural analog of uroguanylin, an endogenous intestinal peptide. It was FDA-approved in January 2017 for chronic idiopathic constipation (CIC) and in January 2018 for irritable bowel syndrome with constipation (IBS-C) in adults. Plecanatide acts locally in the intestinal lumen with minimal systemic absorption, functioning as a guanylate cyclase-C (GC-C) agonist to increase intestinal fluid secretion.
Category: Gastrointestinal / GC-C Agonist. Evidence rating: A (strong human clinical data).
Clinical status: FDA-approved (Trulance for CIC, January 2017; IBS-C, January 2018)
Plecanatide binds to and activates guanylate cyclase-C (GC-C) receptors on the luminal surface of intestinal epithelial cells, primarily in the proximal small intestine. This increases intracellular and extracellular cyclic guanosine monophosphate (cGMP), which activates the cystic fibrosis…
Safety considerations: Most common adverse event: diarrhea (5% in CIC trials, 4.3% in IBS-C trials; severe diarrhea in <1%); Very few systemic side effects due to minimal absorption; Flatulence, abdominal distension, and abdominal tenderness reported in small percentages.
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~1681.9 g/mol |
|---|---|
| CAS number | 467426-54-6 |
| Half-life | Not applicable (acts locally; minimal systemic absorption) |
| Production method | synthetic |
| Anti-doping status | not-listed |
| US regulatory status | FDA-approved. Trulance 3 mg tablets approved January 2017 for CIC; January 2018 for IBS-C in adults. |
Related peptides: Linaclotide.
Both are GC-C agonists approved for CIC and IBS-C. Plecanatide is a uroguanylin analog with pH-dependent binding (optimal at pH 5.0), while linaclotide is a guanylin analog that activates GC-C independent of pH. Clinical efficacy is broadly similar. The diarrhea rate may be slightly lower with plecanatide (5% vs 16-20% for linaclotide), though direct head-to-head comparison data is limited.
No. The FDA includes a black box warning against use in children under 6 years due to the risk of serious dehydration, based on nonclinical juvenile animal studies showing deaths. Use should also be avoided in patients aged 6-17 as safety and efficacy have not been established in this age group.
In clinical trials, improvement in bowel movements was observed as early as the first week of treatment. The full treatment effect develops over the first 2-4 weeks of daily use.