Linaclotide

approved

Also known as: Linzess, Constella

Linaclotide is a 14-amino acid synthetic peptide that acts as a potent agonist of guanylate cyclase-C (GC-C), a receptor expressed on the luminal surface of intestinal epithelial cells. Upon binding, it increases intracellular cyclic guanosine monophosphate (cGMP) levels, which activates the cystic fibrosis transmembrane conductance regulator (CFTR) and promotes chloride and bicarbonate secretion into the intestinal lumen. This ionic flux drives water secretion, accelerating gastrointestinal transit and softening stool. Additionally, elevated cGMP may reduce visceral hypersensitivity by modulating nociceptive signaling, contributing to its analgesic effects in irritable bowel syndrome with constipation (IBS-C). Key research findings from clinical trials demonstrate that linaclotide significantly improves spontaneous bowel movement frequency, stool consistency, and abdominal pain compared to placebo in patients with IBS-C and chronic idiopathic constipation (CIC). A meta-analysis of phase 3 trials confirmed its efficacy, with a number needed to treat of approximately 6 for IBS-C responders. Common adverse effects include diarrhea (up to 20% incidence), which is dose-dependent and often transient. Long-term safety data support sustained efficacy without tachyphylaxis over 12–18 months. Clinically, linaclotide is approved by the FDA and EMA for adults with IBS-C and CIC, typically dosed at 290 µg (IBS-C) or 145 µg (CIC) once daily. It is contraindicated in pediatric patients under 6 years and should be avoided in those with mechanical gastrointestinal obstruction. Its peptide structure limits systemic absorption, confining activity to the gut lumen and reducing off-target effects. For research purposes only — not medical advice.

Key data

Category
Gut & GI
Molecular weight
1526.8 g/mol
Molecular formula
C59H79N15O21S6
CAS number
851199-59-2
Administration
oral
Research status
approved
References
459
Tags
guanylate-cyclase-c, approved, ibs

Research & studies

Management of Chronic Constipation: A Comprehensive Review
Internal medicine (Tokyo, Japan) · 2025 · PubMed

Treatment begins with lifestyle and dietary changes, then progresses to specialized tests or symptom-based classification.; Newer drugs include osmotic laxatives, secretagogues, bile acid transporter inhibitors, probiotics, prokinetics, and Kampo medicines.; Linaclotide is a small peptide agonist of guanylate cyclase C receptors, used for chronic constipation and irritable bowel syndrome.; Linaclotide is not linked to serum enzyme elevations or clinically apparent liver injury.

Linaclotide
2024 · PubMed
Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
The lancet. Gastroenterology & hepatology · 2024 · PubMed
Linaclotide
2024 · PubMed
2022 Seoul Consensus on Clinical Practice Guidelines for Functional Constipation
Journal of neurogastroenterology and motility · 2023 · PubMed
Irritable bowel syndrome
Medicina clinica · 2022 · PubMed

Irritable bowel syndrome is a common functional bowel disorder with significant daily life and economic impacts.; Symptoms include abdominal pain, bloating, distention, and altered bowel movements (diarrhea, constipation, or mixed).; The disease affects 5%-10% of healthy individuals and typically follows a relapsing-remitting course.; Aetiopathogenesis and pathophysiological mechanisms remain unknown.

Recent advances in the treatment of irritable bowel syndrome
Polish archives of internal medicine · 2021 · PubMed
European society of neurogastroenterology and motility guidelines on functional constipation in adults
Neurogastroenterology and motility · 2020 · PubMed

Frequently asked questions

What is Linaclotide?

Linaclotide is a 14-amino acid synthetic peptide that acts as a potent agonist of guanylate cyclase-C (GC-C), a receptor expressed on the luminal surface of intestinal epithelial cells. Upon binding, it increases intracellular cyclic guanosine monophosphate (cGMP) levels, which activates the cystic fibrosis transmembra

How does Linaclotide work?

Guanylate cyclase-C agonist 14-aa peptide that increases intestinal fluid secretion and transit; approved for IBS-C and chronic constipation.

What is the research status of Linaclotide?

Linaclotide is currently classified as approved, with 459 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Linaclotide?

Linaclotide has a molecular weight of approximately 1526.8 g/mol (formula C59H79N15O21S6).

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