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Context, anatomy, and key evidence

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GC-C agonist

Linaclotide

Published evidence · coverage incomplete
Anatomical contextAnatomy connections are not mapped yet.

No body region is highlighted until this profile has a supported anatomical connection. This does not mean the peptide has no biological effects.

Read published mechanism findings ↓

At a glance

What is it—and why does it matter?

The marketed drug substance is specified as linaclotide acetate, with PubChem CID 16158207. The mechanism described links cGMP elevation to activation of the CFTR chloride channel/regulator. Linaclotide is used in irritable bowel syndrome with constipation predominance (IBS-C). The label states a contraindication for age <2 years based on risk of serious dehydration.

Sources for this introduction: [1] [2] [3] [4]

This published profile is a reference in progress. Findings retain their source context; missing topics are marked below.

What is it?

A molecule, not a product name.

Identity

The marketed drug substance is specified as linaclotide acetate, with PubChem CID 16158207.

Sources[2]iuphar-commentsIUPHAR ligand commentaryMarketed formulations contain linaclotide acetate (PubChem CID 16158207 ).
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Marketed formulations contain linaclotide acetate (PubChem CID 16158207 ).”

    IUPHAR ligand commentary · General comments

    iuphar-comments:5017:c3e29070abac:c3e29070abac

How does it work?

Target, response, and disposition.

Mechanism

By activating GC-C (guanylate cyclase 2C) at the luminal surface of intestinal epithelial cells, linaclotide is stated to raise intracellular/epithelial cGMP levels.

Sources[2]iuphar-commentsIUPHAR ligand commentaryLinaclotide activation of guanylate cyclase 2C in the luminal aspect of intestinal epithelium causes increased cGMP levels
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Linaclotide activation of guanylate cyclase 2C in the luminal aspect of intestinal epithelium causes increased cGMP levels”

    IUPHAR ligand commentary · Mechanism of action

    iuphar-comments:5017:c3e29070abac:c3e29070abac

Mechanism

CFTR is described as regulating chloride ion efflux in enterocytes of the gastrointestinal tract.

Sources[2]iuphar-commentsIUPHAR ligand commentarywhich controls chloride ion efflux from enterocytes lining the GI tract.
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “which controls chloride ion efflux from enterocytes lining the GI tract.”

    IUPHAR ligand commentary · Mechanism of action

    iuphar-comments:5017:c3e29070abac:c3e29070abac

Mechanism

The mechanism described links cGMP elevation to activation of the CFTR chloride channel/regulator.

Sources[2]iuphar-commentsIUPHAR ligand commentaryand this causes activation of the cystic fibrosis transmembrane conductance regulator (CFTR),
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “and this causes activation of the cystic fibrosis transmembrane conductance regulator (CFTR),”

    IUPHAR ligand commentary · Mechanism of action

    iuphar-comments:5017:c3e29070abac:c3e29070abac

Mechanism

Downstream of CFTR-mediated ion transport, the stated physiologic result is increased water movement into the intestinal lumen, producing stool softening and promoting bowel movements.

Sources[2]iuphar-commentsIUPHAR ligand commentaryThe result is a net efflux of water into the intestinal lumen which softens stools and stimulates bowel movements [Reference 24736] [Reference 24734].
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “The result is a net efflux of water into the intestinal lumen which softens stools and stimulates bowel movements [Reference 24736] [Reference 24734].”

    IUPHAR ligand commentary · Mechanism of action

    iuphar-comments:5017:c3e29070abac:c3e29070abac

Pharmacokinetics

The pharmacokinetics section states negligible systemic availability after oral administration, with linaclotide and active metabolite plasma concentrations below the assay’s quantitation limit at 72/145/290 mcg doses.

Sources[1]dailymedThese highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012LINZESS is minimally absorbed with negligible systemic availability following oral administration. Concentrations of linaclotide and its active metabolite in plasma are below the limit of quantitation after oral doses of 72 mcg, 145 mcg, or 290 mcg were administered.
Source records
1
Regulatory records
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “LINZESS is minimally absorbed with negligible systemic availability following oral administration. Concentrations of linaclotide and its active metabolite in plasma are below the limit of quantitation after oral doses of 72 mcg, 145 mcg, or 290 mcg were administered.”

    These highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012 · 12.3Pharmacokinetics

    dailymed:09beda19-56d6-4a56-afdc-9a77b70b2ef3:91867a505c42:91867a505c42

What has been studied?

What the evidence says.

Study findings

Linaclotide is used in irritable bowel syndrome with constipation predominance (IBS-C).

Sources[2]iuphar-commentsIUPHAR ligand commentaryUsed to treat chronic constipation and irritable bowel syndrome (IBS) where constipation is the main symptom (IBS-C).
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Used to treat chronic constipation and irritable bowel syndrome (IBS) where constipation is the main symptom (IBS-C).”

    IUPHAR ligand commentary · Clinical use

    iuphar-comments:5017:c3e29070abac:c3e29070abac

Study findings

An in-source fragmentation artifact (n=1) in linaclotide digest data was excluded using diagnostic neutral losses and retention-time alignment criteria.

Sources[3]pubmedRapid and comprehensive identification of the metabolic soft spots of peptide drugs with highly cross-linked disulfide bonds by integrating established proteomic workflow with a product ion filtering strategy.From linaclotide digests, 3 peptic fragments were confidently identified, whereas 1 in-source fragmentation artifact was excluded based on diagnostic neutral losses and retention time alignment.
Reported result
1 in-source fragmentation artifact excluded
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “From linaclotide digests, 3 peptic fragments were confidently identified, whereas 1 in-source fragmentation artifact was excluded based on diagnostic neutral losses and retention time alignment.”

    Rapid and comprehensive identification of the metabolic soft spots of peptide drugs with highly cross-linked disulfide bonds by integrating established proteomic workflow with a product ion filtering strategy. · Abstract

    pubmed:42612545:9fe585b8b73a:9fe585b8b73a

Study findings

Clinically, linaclotide is used for the treatment of chronic constipation.

Sources[2]iuphar-commentsIUPHAR ligand commentaryUsed to treat chronic constipation and irritable bowel syndrome (IBS) where constipation is the main symptom (IBS-C).
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Used to treat chronic constipation and irritable bowel syndrome (IBS) where constipation is the main symptom (IBS-C).”

    IUPHAR ligand commentary · Clinical use

    iuphar-comments:5017:c3e29070abac:c3e29070abac

Study findings

Analysis of linaclotide digests yielded confident identification of 3 peptic fragments.

Sources[3]pubmedRapid and comprehensive identification of the metabolic soft spots of peptide drugs with highly cross-linked disulfide bonds by integrating established proteomic workflow with a product ion filtering strategy.From linaclotide digests, 3 peptic fragments were confidently identified, whereas 1 in-source fragmentation artifact was excluded based on diagnostic neutral losses and retention time alignment.
Reported result
3 peptic fragments confidently identified
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “From linaclotide digests, 3 peptic fragments were confidently identified, whereas 1 in-source fragmentation artifact was excluded based on diagnostic neutral losses and retention time alignment.”

    Rapid and comprehensive identification of the metabolic soft spots of peptide drugs with highly cross-linked disulfide bonds by integrating established proteomic workflow with a product ion filtering strategy. · Abstract

    pubmed:42612545:9fe585b8b73a:9fe585b8b73a

Risks and interactions

Risks, organized for scanning.

Contraindications

The label states a contraindication for age <2 years based on risk of serious dehydration.

Sources[1]dailymedThese highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012LINZESS is contraindicated in:Patients less than 2 years of age due to the risk of serious dehydration
Source records
1
Regulatory records
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “LINZESS is contraindicated in:Patients less than 2 years of age due to the risk of serious dehydration”

    These highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012 · 4CONTRAINDICATIONS

    dailymed:09beda19-56d6-4a56-afdc-9a77b70b2ef3:91867a505c42:91867a505c42

Interactions

The label explicitly states that drug–drug interaction studies have not been conducted for LINZESS.

Sources[1]dailymedThese highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012No drug-drug interaction studies have been conducted with LINZESS.
Source records
1
Regulatory records
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “No drug-drug interaction studies have been conducted with LINZESS.”

    These highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012 · 12.3Pharmacokinetics

    dailymed:09beda19-56d6-4a56-afdc-9a77b70b2ef3:91867a505c42:91867a505c42

Products and regulatory status

Same ingredient. Different records.

Regulatory status

The labeled indication includes irritable bowel syndrome with constipation (IBS-C) for adults and pediatric patients 7 years of age and older.

Sources[1]dailymedThese highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012LINZESS is indicated for the treatment of:• irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older
Source records
1
Regulatory records
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “LINZESS is indicated for the treatment of:• irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older”

    These highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012 · 1INDICATIONS AND USAGE

    dailymed:09beda19-56d6-4a56-afdc-9a77b70b2ef3:91867a505c42:91867a505c42

Administration context

The practical clinical context.

Dose records

For adult chronic idiopathic constipation, the label recommends 145 mcg QD, with an option of 72 mcg QD based on clinical presentation or tolerability.

Sources[1]dailymedThese highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012Chronic Idiopathic Constipation (CIC)inAdultsThe recommended dosage of LINZESS in adults is 145 mcg orally once daily. A dosage of 72 mcg once daily may be used based on individual presentation or tolerability.
Source records
1
Regulatory records
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Chronic Idiopathic Constipation (CIC)inAdultsThe recommended dosage of LINZESS in adults is 145 mcg orally once daily. A dosage of 72 mcg once daily may be used based on individual presentation or tolerability.”

    These highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012 · 2.1Recommended Dosage

    dailymed:09beda19-56d6-4a56-afdc-9a77b70b2ef3:91867a505c42:91867a505c42

Research status + gaps

What still needs better answers?

  • No publishable claim yet for: administration, safety
  • 82 compiled claim(s) withheld by automated assurance: assurance_score_below_0.58 (52), assurance_score_below_0.72 (27), current_regulatory_source_required (13), extraction_ambiguity (54), extraction_confidence_not_high (1), high_risk_requires_regulatory_or_two_independent_sources (28), no_direct_support (78)

These are the limits of this profile, not an exhaustive list of scientific uncertainties.

References + discovery

Open the records yourself.

  1. These highlights do not include all the information needed to useLINZESSsafely and effectively.See full prescribing information forLINZESS.LINZESS®(linaclotide)capsules, for oral useInitial U.S. Approval:2012 ↗

    dailymed · published 2026-05-21 · retrieved 2026-09-04T22:09:14Z

  2. IUPHAR ligand commentary ↗

    iuphar-comments · published 2026-08-27 · retrieved 2026-08-27T11:48:55Z

  3. Rapid and comprehensive identification of the metabolic soft spots of peptide drugs with highly cross-linked disulfide bonds by integrating established proteomic workflow with a product ion filtering strategy. ↗

    pubmed · published 2026-07-17 · retrieved 2026-08-27T11:48:55Z

Publication history and provenance

Version 3 · Automated assessment · 2026-09-04T22:09:14Z

d6f6aed102fa0e392cd1e36f1c63e639f97bf1e8e69d8d4d114f4620e9bf0010