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Description

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.6 nM [Ki]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
Metabolic and toxicological considerations for the latest drugs used to treat irritable bowel syndrome.
2013 Apr
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 Jan
Patents

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.
Name Type Language
LINACLOTIDE
DASH   INN   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
LINACLOTIDE [JAN]
Common Name English
LINACLOTIDE [USAN]
Common Name English
ASP-0456
Code English
LINACLOTIDE [INN]
Common Name English
LINACLOTIDE [MI]
Common Name English
LINACLOTIDE [WHO-DD]
Common Name English
LINACLOTIDE [ORANGE BOOK]
Common Name English
(9-L-TYROSINE)HEAT-STABLE ENTEROTOXIN (ESCHERICHIA COLI)-(6-19)-PEPTIDE
Common Name English
MD-1100
Code English
ASP0456
Code English
LINACLOTIDE [VANDF]
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)
Common Name English
LINZESS
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C548
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
WHO-ATC A06AX04
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
WHO-VATC QA06AX04
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
LIVERTOX 557
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
NDF-RT N0000185500
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
Code System Code Type Description
WIKIPEDIA
LINACLOTIDE
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
IUPHAR
5017
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
CAS
851199-59-2
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
DRUG BANK
DB08890
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
INN
8802
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
ChEMBL
CHEMBL3301675
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
HSDB
851199-59-2
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
PUBCHEM
16158208
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
MERCK INDEX
M6818
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY Merck Index
NDF-RT
N0000185499
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY Guanylate Cyclase Activators [MoA]
EVMPD
SUB32529
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
LactMed
851199-59-2
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
NCI_THESAURUS
C81001
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
MESH
C523483
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY
RXCUI
1307404
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY RxNorm
EPA CompTox
851199-59-2
Created by admin on Tue Oct 22 01:38:06 UTC 2019 , Edited by admin on Tue Oct 22 01:38:06 UTC 2019
PRIMARY