Linaclotide
Linaclotide
Overview
Linaclotide is a synthetic 14-amino-acid peptide agonist of guanylate cyclase-C (GC-C) receptors in the intestinal epithelium FDA-approved under the brand name Linzess for irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation. It represents one of the few gut peptides with full FDA approval and a robust clinical evidence base from multiple large Phase 3 trials. Linaclotide acts locally in the gut with minimal systemic absorption making it a highly targeted gastrointestinal therapeutic.
Mechanism of Action
Linaclotide mimics the heat-stable enterotoxins produced by E. coli binding to and activating guanylate cyclase-C receptors on intestinal epithelial cells. GC-C activation increases intracellular cGMP which activates CFTR chloride channels promoting chloride and bicarbonate secretion into the intestinal lumen. This osmotic effect increases luminal fluid content softening stool and accelerating intestinal transit. The elevated cGMP also has direct analgesic effects — it diffuses through the epithelium to afferent pain-sensing neurons reducing their sensitivity to colonic distension and explaining linaclotide's efficacy for abdominal pain in IBS-C beyond its laxative effects. Minimal systemic absorption means virtually no off-target effects.
Dosage Information
Typical Dose
72-290 mcg once daily (FDA-approved doses)
Frequency
Once daily on empty stomach 30 minutes before first meal
Administration
Oral capsule
Notes
FDA-approved for IBS-C (290 mcg) and chronic idiopathic constipation (72 mcg or 145 mcg). Must be taken on empty stomach. Keep away from children — dangerous if accidentally ingested.
Where does Linaclotide sit?
See how this peptide compares across all 111 peptides in our database.
Evidence Score
0.80
Compound Data
Molecular Formula
C59H79N15O21S6
Molecular Weight
1526.80 g/mol
IUPAC Name
(2S)-2-[[(1R,4S,7S,13S,16R,21R,24R,27S,30S,33R,38R,44S)-21-amino-13-(2-amino-2-oxoethyl)-27-(2-carboxyethyl)-44-[(1R)-1-hydroxyethyl]-30-[(4-hydroxyphenyl)methyl]-4-methyl-3,6,12,15,22,25,28,31,40,43,46,51-dodecaoxo-18,19,35,36,48,49-hexathia-2,5,11,14,23,26,29,32,39,42,45,52-dodecazatetracyclo[22.22.4.216,33.07,11]dopentacontane-38-carbonyl]amino]-3-(4-hydroxyphenyl)propanoic acid
PubChem CID
16158208Potential Side Effects
Community Experiences
No experiences shared yet. Be the first!
Quick Facts
- Administration
- Oral capsule
- Typical Dose
- 72-290 mcg once daily (FDA-approved doses)
- Frequency
- Once daily on empty stomach 30 minutes before first meal
- References
- 0 curated + 49 from PubMed
- Clinical Trials
- 50 registered
- Evidence Score
- 0.8 / 100