Plecanatide
approvedAlso known as: Trulance
**Mechanism of Action** Plecanatide is a synthetic analog of uroguanylin, a endogenous peptide that activates guanylate cyclase-C (GC-C) receptors on the luminal surface of intestinal epithelial cells. This activation increases intracellular cyclic guanosine monophosphate (cGMP) levels, leading to enhanced chloride and bicarbonate secretion via the cystic fibrosis transmembrane conductance regulator (CFTR). The resulting increase in intestinal fluid secretion and accelerated transit is pH-dependent, with optimal activity in the acidic environment of the proximal small intestine, mimicking the physiological regulation of fluid homeostasis. **Key Research Findings** Clinical trials (e.g., NCT01983358, NCT01983371) demonstrated significant improvements in spontaneous bowel movement frequency and stool consistency in patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). A 12-week phase III study reported 21% of CIC patients achieving ≥3 complete spontaneous bowel movements per week versus 8% with placebo. Unlike lubiprostone, plecanatide does not require active transport for absorption and exhibits minimal systemic bioavailability (<0.1%), reducing off-target effects. **Clinical Relevance** Approved by the FDA in 2017 (Trulance®) for CIC and IBS-C, plecanatide offers a targeted, locally acting therapy with a favorable safety profile. Common adverse effects include diarrhea (5–16%) and abdominal distension. Its pH-dependent activation may reduce the risk of electrolyte imbalances compared to non-selective secretagogues. For research purposes only — not medical advice.
Key data
C65H104N18O26S4Research & studies
Durable overall CSBM response rate was 23.5% with plecanatide vs 10.2% with placebo (p < 0.001).; Plecanatide increased mean weekly CSBM (1.89 vs 0.9) and SBM (2.33 vs 1.03) compared to placebo.; Diarrhea occurred in 4.3% of plecanatide patients vs 0.6% of placebo patients (p = 0.002).; Weekly CSBM response at week 2 and baseline stool consistency were predictors of durable overall response.
Strong recommendations were made for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride.; Conditional recommendations were made for fiber, lactulose, senna, magnesium oxide, and lubiprostone.; The guideline emphasizes shared decision-making based on patient preferences, cost, and availability.; Evidence gaps are highlighted to guide future research.
Strong recommendations were made for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride.; Conditional recommendations were made for fiber, lactulose, senna, magnesium oxide, and lubiprostone.; Plecanatide is not absorbed and is not expected to cause adverse effects in breastfed infants.; Guidelines emphasize shared decision-making based on patient preferences, cost, and availability.
Frequently asked questions
What is Plecanatide?
**Mechanism of Action** Plecanatide is a synthetic analog of uroguanylin, a endogenous peptide that activates guanylate cyclase-C (GC-C) receptors on the luminal surface of intestinal epithelial cells. This activation increases intracellular cyclic guanosine monophosphate (cGMP) levels, leading to enhanced chloride and
How does Plecanatide work?
Uroguanylin-analog GC-C agonist that promotes pH-dependent intestinal fluid secretion; approved for chronic idiopathic constipation and IBS-C.
What is the research status of Plecanatide?
Plecanatide is currently classified as approved, with 124 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Plecanatide?
Plecanatide has a molecular weight of approximately 1681.9 g/mol (formula C65H104N18O26S4).
Related peptides
Guanylate cyclase-C agonist 14-aa peptide that increases intestinal fluid secretion and transit; approved for IBS-C and chronic constipation.
GLP-2 receptor agonist that promotes intestinal mucosal growth and absorption; approved for short bowel syndrome.
Tight-junction-regulating octapeptide that reduces intestinal permeability ('leaky gut'); trialed as an adjunct for celiac disease.
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