Gut HealthWell-evidencedHuman trials

Plecanatide

Plecanatide

Overview

Plecanatide is a synthetic analog of uroguanylin — an endogenous gut peptide that regulates fluid secretion in the intestine — FDA-approved under the brand name Trulance for chronic idiopathic constipation and IBS-C. It acts as a GC-C receptor agonist similar to linaclotide but is designed to be pH-sensitive activating preferentially in the acidic environment of the proximal small intestine where uroguanylin naturally acts. This pH-sensitivity may produce a more physiological pattern of activity compared to linaclotide.

Mechanism of Action

Plecanatide binds to and activates guanylate cyclase-C receptors with pH-dependent potency — it is more active at the lower pH (approximately 5.5) of the duodenum and proximal jejunum mimicking the natural activation profile of uroguanylin. GC-C activation increases intracellular cGMP driving CFTR-mediated chloride and bicarbonate secretion increasing luminal fluid and accelerating intestinal transit. The pH-sensitivity means peak activity occurs in the proximal small intestine where absorption of the secreted fluid is still possible reducing the diarrhea risk compared to colon-targeted approaches. Like linaclotide elevated cGMP also reduces visceral hypersensitivity explaining efficacy for abdominal pain.

Dosage Information

Typical Dose

3 mg once daily

Frequency

Once daily with or without food

Anytime

Administration

Oral tablet

Notes

FDA-approved 3mg dose. Can be taken with food unlike linaclotide. Tablet can be crushed and mixed with applesauce for patients who have difficulty swallowing.

Where does Plecanatide sit?

See how this peptide compares across all 111 peptides in our database.

Evidence Score

0.78

Clinical trials
1.0035%
Literature
0.9530%
Community
0.0020%
Completeness
1.0015%
10 RCTs1 clinical trials15 reviews

Compound Data

Plecanatide structure

Molecular Formula

C65H104N18O26S4

Molecular Weight

1681.90 g/mol

IUPAC Name

(2S)-2-[[(1R,4S,7S,10S,13S,16R,19S,22S,25R,32S,38R)-10-(2-amino-2-oxoethyl)-25-[[(2S)-4-carboxy-2-[[(2S)-3-carboxy-2-[[(2S)-2,4-diamino-4-oxobutanoyl]amino]propanoyl]amino]butanoyl]amino]-22-(2-carboxyethyl)-32-[(1R)-1-hydroxyethyl]-4-methyl-19-(2-methylpropyl)-3,6,9,12,15,18,21,24,30,33,36-undecaoxo-7,13-di(propan-2-yl)-27,28,40,41-tetrathia-2,5,8,11,14,17,20,23,31,34,37-undecazabicyclo[14.13.13]dotetracontane-38-carbonyl]amino]-4-methylpentanoic acid

PubChem CID

70693500

Potential Side Effects

Diarrhea (common)Abdominal distension (uncommon)Nausea (uncommon)Sinusitis (uncommon in trials)

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Quick Facts

Administration
Oral tablet
Typical Dose
3 mg once daily
Frequency
Once daily with or without food
References
0 curated + 44 from PubMed
Clinical Trials
13 registered
Evidence Score
0.8 / 100