Linaclotide

Summary

Linaclotide (CHEMBL3301675) is an approved protein guanylate cyclase 2C agonist (ATC A06AX04) targeting GUCY2C; indicated across 5 conditions including irritable bowel syndrome and constipation disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Protein
• ATC class: A06AX04
• Targets: 1 (GUCY2C)
• Indications: 5 conditions
• Clinical trials: 41
• Chemistry: 1526.8 Da · C59H79N15O21S6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3301675
Name	Linaclotide
Type	Protein
Max phase	4
FDA approved	yes
PubChem CID	16158208
ChEBI	CHEBI:68551
ATC	A06AX04
Molecular formula	C59H79N15O21S6
Molecular weight	1526.8
InChIKey	KXGCNMMJRFDFNR-WDRJZQOASA-N

SMILES: C[C@H]1C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)CNC(=O)[C@@H](NC2=O)[C@@H](C)O)C(=O)N[C@@H](CC4=CC=C(C=C4)O)C(=O)O)C(=O)N[C@@H](CSSC[C@@H](C(=O)N3)N)C(=O)N[C@H](C(=O)N5CCC[C@H]5C(=O)N1)CC(=O)N)CC6=CC=C(C=C6)O)CCC(=O)O

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

ChEBI definition: A fourteen-membered heterodetic cyclic peptide consisting of Cys, Cys, Glu, Tyr, Cys, Cys, Asn, Pro, Ala, Cys, Thr, Gly, Cys and Tyr residues joined in sequence and cyclised by three disulfide bonds: between Cys1 and Cys6, between Cys2 and Cys10, and between Cys5 and Cys13. Used for treatment of irritable bowel syndrome accompanied by constipation.

Pharmacological roles (ChEBI): guanylate cyclase 2C agonist.

Also known as: ASP-0456, ASP0456, Constella, Linaclotida, Linaclotide, Linzess, MD-1100, MD-7246 (DELAYED RELEASE FORMULATION), LINACLOTIDE, linaclotide

Parent form; salt/anhydrous children: CHEMBL3301676

Patent coverage: 458 distinct patent families (1,075 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
GUCY2C	Guanylyl cyclase-C	Agonist	8.91	0%	P25092

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Sodium-dependent dopamine transporter.

Bioactivity

ChEMBL activities: 1 potent at pChembl ≥ 5 of 1 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SLC6A3	6.89	AC50	130	nM	CHEMBL_ACT_25123925

Target pathways

Aggregated over 1 target gene(s): GUCY2C.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Digestion	1	GUCY2C
Intestinal infectious diseases	1	GUCY2C

Dominant GO biological processes

GO term	Targets
cGMP biosynthetic process	1
receptor guanylyl cyclase signaling pathway	1
response to toxic substance	1
intracellular signal transduction	1
regulation of cell population proliferation	1
protein phosphorylation	1
cyclic nucleotide biosynthetic process	1

Indications & clinical

Indications

5 indications (3 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
irritable bowel syndrome	4	MONDO:0005052	EFO:0000555
constipation disorder	4	MONDO:0002203	HP:0002019
colorectal adenoma	2	MONDO:0005484	EFO:0005406
colorectal carcinoma	2	MONDO:0024331	EFO:1001951

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 41.

Phase distribution

Phase	Trials
PHASE3	14
Not specified	8
PHASE4	7
PHASE2	7
PHASE1	4
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06748638	PHASE4	ENROLLING_BY_INVITATION	Clinical Study on the Application of Lactulose Combined with Linaclotide in Bowel Preparation for Colonoscopy
NCT07431957	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Linaclotide in Chronic Constipation
NCT02465385	PHASE4	COMPLETED	Single-dose Linaclotide for Capsule Endoscopy Preparation
NCT02590432	PHASE4	COMPLETED	An Open-Label, Long-term Study to Assess the Immunogenicity of LINZESS® (Linaclotide) Administered Orally to Adult Participants With Irritable Bowel Syndrome With Constipation or Chronic Idiopathic Constipation
NCT02837783	PHASE4	TERMINATED	A Study of the Effect of Linaclotide on Abdominal Girth in Participants With Irritable Bowel Syndrome With Constipation (IBS-C)
NCT05134584	PHASE4	UNKNOWN	Efficacy of Linaclotide in Patients With Overlapping Functional Gastrointestinal Disorders
NCT06989268	PHASE4	COMPLETED	Effect to Linaclotide on Colonic Motility
NCT00730015	PHASE3	COMPLETED	Trial of Linaclotide in Patients With Chronic Constipation
NCT00730171	PHASE3	COMPLETED	An Open-label, Long-term Safety Study of Linaclotide in Patients With Chronic Constipation or Irritable Bowel Syndrome With Constipation
NCT00765882	PHASE3	COMPLETED	Phase III, Randomized, Double-Blind, Placebo-Controlled, Trial of Linaclotide Administered to Patients With Chronic Constipation
NCT00765999	PHASE3	COMPLETED	An Open-Label, Long-Term Safety Study of Linaclotide in Patients With Chronic Constipation or Irritable Bowel Syndrome With Constipation
NCT00948818	PHASE3	COMPLETED	Trial of Linaclotide Administered to Patients With Irritable Bowel Syndrome With Constipation
NCT01642914	PHASE3	COMPLETED	Safety and Efficacy of Linaclotide in Patients With Chronic Constipation and Prominent Abdominal Bloating
NCT01880424	PHASE3	COMPLETED	A Phase 3, International, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Irritable Bowel Syndrome With Constipation (IBS-C)
NCT02291679	PHASE3	COMPLETED	Trial of Linaclotide in Patients With Chronic Idiopathic Constipation
NCT02316899	PHASE3	COMPLETED	Phase III Study to Evaluate the Efficacy and Safety of ASP0456 in Patients With Constipation Predominant Irritable Bowel Syndrome
NCT02809105	PHASE3	COMPLETED	A Study of Oral Dosing of ASP0456 in Patients With Chronic Constipation
NCT03573908	PHASE3	COMPLETED	A Trial of Linaclotide 290 μg in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)
NCT04026113	PHASE3	COMPLETED	Linaclotide Safety and Efficacy in Pediatric Participants, 6 to 17 Years of Age, With Irritable Bowel Syndrome With Constipation (IBS-C) or Functional Constipation (FC)
NCT04804267	PHASE3	UNKNOWN	Evaluation of Clinical Equivalence Between Two Linaclotide Products in the Treatment of Chronic Idiopathic Constipation
NCT05652205	PHASE3	COMPLETED	A Study to Assess Adverse Events and Change in Symptoms With Linaclotide Versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, With Functional Constipation
NCT03796884	PHASE2	ACTIVE_NOT_RECRUITING	Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer
NCT01714843	PHASE2	COMPLETED	A Study to Evaluate the Effect of ASP0456 in Patients With Constipation Predominant Irritable Bowel Syndrome
NCT02270983	PHASE2	COMPLETED	Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered to Patients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain
NCT02425722	PHASE2	COMPLETED	A Study to Evaluate Dose Responses of Efficacy and Safety of ASP0456 in Patient With Chronic Constipation
NCT02559206	PHASE2	COMPLETED	Trial of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)
NCT04110145	PHASE2	COMPLETED	Linaclotide Safety and Efficacy in 2 to 5-Year-Old Participants With Functional Constipation
NCT05760313	PHASE2	COMPLETED	A Study to Assess Adverse Events and Change in Disease Activity in Pediatric Participants (Age 6 Months to <2 Years) With Functional Constipation Who Are Treated With Linaclotide
NCT01279915	PHASE1	COMPLETED	A Safety and Pharmacokinetics Study of ASP0456 in Healthy Subjects
NCT01427387	PHASE1	COMPLETED	A Study to Evaluate Safety of Multiple Dose of ASP0456 in Healthy Subjects
NCT02220348	PHASE1	COMPLETED	A Lactation Study in Women Who Are Breastfeeding or Pumping and Are Receiving Linaclotide Therapeutically
NCT05107219	PHASE1	COMPLETED	GCC Agonist Signal in the Small Intestine
NCT07569419	EARLY_PHASE1	RECRUITING	Proof of Principle Study for an Efficacy Trial of Linaclotide for Cystic Fibrosis
NCT02078323	Not specified	COMPLETED	Investigation of Linaclotide’s Effect on the Bi-directional Brain and Gut Axis in IBS-C Patients
NCT02239510	Not specified	TERMINATED	Efficacy of Linaclotide to Senna for CIC
NCT02360384	Not specified	UNKNOWN	Caecal pH as a Biomarker for Irritable Bowel Syndrome
NCT03471728	Not specified	COMPLETED	Post-marketing Surveillance of Linaclotide Tablet in Patients With Irritable Bowel Syndrome With Constipation or Chronic Constipation (Excluding Constipation Due to Organic Diseases)
NCT05137145	Not specified	UNKNOWN	Effect and Safety of Polyethylene Glycol Combined With Linaclotide on Colon Cleansing for Patients With Chronic Constipation
NCT05291325	Not specified	COMPLETED	Application of Linaclotide Capsule in Bowel Preparation for Colonoscopy
NCT05379491	Not specified	COMPLETED	Application of Linaclotide Capsule in Bowel Preparation for Patients at High Risk of Inadequate Bowel Preparation

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).