LINACLOTIDE ACETATE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202811s011lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/23090647

Linaclotide (marketed under the trade name Linzess and Constella) is a peptide agonist of the guanylate cyclase 2C (GC-C). Once linaclotide and its active metabolite binds to GC-C, it has local effect on the luminal surface of the intestinal epithelium. Activation of GC-C by linaclotide results in the intra- and extracellular increase of cyclic guanosine monophosphate concentrations (cGMP). This elevation of cGMP levels stimulates the secretion of chloride and bicarbonate into the intestinal lumen via activation of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. The metabolite of linaclotide MM-419447 (CCEYCCNPACTGC) contributes to the pharmacologic effects of linaclotide. Ultimately, linaclotide helps patients with IBS (especially with constipation) as GI transit is accelerated and the release of intestinal fluid is increased. In animal models, a decrease in visceral pain after administration of linaclotide may be observed. A decrease in the activity of pain-sensing nerves occurs as a result of an increase in extracellular cGMP. It was approved by the FDA in August 2012 for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C) in adults.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Heat-stable enterotoxin receptor 3 Target ID: CHEMBL1795197 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202811s011lbl.pdf	Agonist 2752		2.6 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Irritable bowel syndrome 61 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202811s011lbl.pdf	Primary		Approved 8583	LINZESS Approved Use Indicated in adults for treatment of: Irritable bowel syndrome with constipation (IBS-C) (1.1) Chronic idiopathic constipation (CIC) (1.2) Launch Date 2012
Constipation 112 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202811s011lbl.pdf	Curative		Approved 8583	LINZESS Approved Use Indicated in adults for treatment of: Irritable bowel syndrome with constipation (IBS-C) (1.1) Chronic idiopathic constipation (CIC) (1.2) Launch Date 2012

PubMed

Title	Date	PubMed
Metabolic and toxicological considerations for the latest drugs used to treat irritable bowel syndrome.	2013-04	23330973
Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.	2013-01	23090647

Patents

Sample Use Guides

In Vivo Use Guide

In case of Irritable bowel syndrome with constipation: 290 ug orally once daily. In case of Chronic idiopathic constipation: 145 ug orally once daily. Take on empty stomach at least 30 minutes prior to first meal of the day.

Route of Administration: Oral

In Vitro Use Guide

0.01 to 1,000 nM linaclotide was used in a competitive radioligand binding assays using T84 cells and [125I]pSTa. Human T84 cells were incubated at pH 7 for 1 hour at 37°C with [125I]-pSTa and increasing concentrations of linaclotide.

Substance Class	Protein Created by `admin` on `Mon Mar 31 20:39:45 GMT 2025` Edited by `admin` on `Mon Mar 31 20:39:45 GMT 2025`
Protein Sub Type
Sequence Type	COMPLETE
Record UNII	NSF067KU1M
Record Status	`FAILED`
Record Version

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Name

Type

Language

LINACLOTIDE ACETATE

Official Name

English

MD-1100 ACETATE

Preferred Name

English

L-TYROSINE, L-CYSTEINYL-L-CYSTEINYL-L-.ALPHA.-GLUTAMYL-L-TYROSYL-L-CYSTEINYL-L-CYSTEINYL-L-ASPARAGINYL-L-PROLYL-L-ALANYL-L-CYSTEINYL-L-THREONYLGLYCYL-L-CYSTEINYL-, CYCLIC (1->6),(2->10),(5->13)-TRIS(DISULPHIDE), MONOACETATE (SALT)

Common Name

English

LINACLOTIDE ACETATE [MART.]

Common Name

English

L-TYROSINE, L-CYSTEINYL-L-CYSTEINYL-L-.ALPHA.-GLUTAMYL-L-TYROSYL-L-CYSTEINYL-L-CYSTEINYL-L-ASPARAGINYL-L-PROLYL-L-ALANYL-L-CYSTEINYL-L-THREONYLGLYCYL-L-CYSTEINYL-, CYCLIC (1->6),(2->10),(5->13)-TRIS(DISULFIDE), MONOACETATE (SALT)

Common Name

English

L-CYSTEINYL-L-CYSTEINYL-L-.ALPHA.-GLUTAMYL-L-TYROSYL-L-CYSTEINYL-L-CYSTEINYL-L-ASPARAGINYL-L-PROLYL-L-ALANYL-L-CYSTEINYL-L-THREONYLGLYCYL-L-CYSTEINYL-L-TYROSINE CYCLIC (1->6),(2->10),(5->13)-TRIS(DISULFIDE) MONOACETATE (SALT)

Common Name

English

L-CYSTEINYL-L-CYSTEINYL-L-.ALPHA.-GLUTAMYL-L-TYROSYL-L-CYSTEINYL-L-CYSTEINYL-L-ASPARAGINYL-L-PROLYL-L-ALANYL-L-CYSTEINYL-L-THREONYLGLYCYL-L-CYSTEINYL-L-TYROSINE CYCLIC (1->6),(2->10),(5->13)-TRIS(DISULPHIDE) MONOACETATE (SALT)

Common Name

English

MM-416775

Code

English

LINACLOTIDE ACETATE [USAN]

Common Name

English

LINACLOTIDE ACETATE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C548