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Description
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

Curator's Comment: Linaclotide was discovered by scientists at Ironwood and is marketed in Europe by Almirall through a license agreement between the two companies. Constella® is a trademark owned by Ironwood Pharmaceuticals, Inc.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.6 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1.34628481E12
Curative
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

1.34628481E12
PubMed

PubMed

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

Patents

Sample Use Guides

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 Sat Dec 16 00:43:21 UTC 2023
Edited
by admin
on Sat Dec 16 00:43:21 UTC 2023
Protein Sub Type
Sequence Type COMPLETE
Record UNII
NSF067KU1M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LINACLOTIDE ACETATE
MART.   MI   USAN  
USAN  
Official 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
MD-1100 ACETATE
Code English
LINACLOTIDE ACETATE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C548
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
Code System Code Type Description
MERCK INDEX
m6818
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
PRIMARY Merck Index
EPA CompTox
DTXSID60583223
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
PRIMARY
CAS
851199-60-5
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
PRIMARY
ChEMBL
CHEMBL3301675
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
PRIMARY
NCI_THESAURUS
C77223
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
PRIMARY
USAN
RR-137
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
PRIMARY
PUBCHEM
16158207
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
PRIMARY
FDA UNII
NSF067KU1M
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
PRIMARY
DRUG BANK
DBSALT000108
Created by admin on Sat Dec 16 00:43:21 UTC 2023 , Edited by admin on Sat Dec 16 00:43:21 UTC 2023
PRIMARY
Related Record Type Details
STARTING MATERIAL -> INGREDIENT
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
MOL_WEIGHT:NUMBER(CALCULATED) CHEMICAL
Molecular Formula CHEMICAL