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
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
Compound Data
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
70693500Potential Side Effects
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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