linaclotide   Click here for help

GtoPdb Ligand ID: 5017

Synonyms: Constella® | Linzess® | MM-416775
Approved drug
linaclotide is an approved drug (FDA and EMA (2012))
Compound class: Peptide
Comment: Linaclotide represents a first-in-class, oral guanylate cyclase 2C activator [2]. It is a synthetic analogue of pathological heat-stable bacterial enterotoxins, and retains the same intrachain disulfide bond structure essential for biological activity.
Marketed formulations contain linaclotide acetate (PubChem CID 16158207). See also plecanatide, the second approved GC-C activator.
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Ligand Activity Visualisation Charts

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View more information in the IUPHAR Pharmacology Education Project: linactolide

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES OC(=O)CC[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](C)NC(=O)[C@H]4N(C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC1=O)Cc1ccc(cc1)O)CSSC[C@H](NC(=O)CNC(=O)[C@@H](NC3=O)[C@H](O)C)C(=O)N[C@H](C(=O)O)Cc1ccc(cc1)O)CSSC[C@@H](C(=O)N2)N)CC(=O)N)CCC4
Isomeric 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](Cc2ccc(cc2)O)C(=O)O)C(=O)N[C@@H](CSSC[C@@H](C(=O)N3)N)C(=O)N[C@H](C(=O)N2CCC[C@H]2C(=O)N1)CC(=O)N)Cc1ccc(cc1)O)CCC(=O)O
InChI InChI=1S/C59H79N15O21S6/c1-26-47(82)69-41-25-101-99-22-38-52(87)65-33(13-14-45(80)81)49(84)66-34(16-28-5-9-30(76)10-6-28)50(85)71-40(54(89)72-39(23-97-96-20-32(60)48(83)70-38)53(88)67-35(18-43(61)78)58(93)74-15-3-4-42(74)56(91)63-26)24-100-98-21-37(64-44(79)19-62-57(92)46(27(2)75)73-55(41)90)51(86)68-36(59(94)95)17-29-7-11-31(77)12-8-29/h5-12,26-27,32-42,46,75-77H,3-4,13-25,60H2,1-2H3,(H2,61,78)(H,62,92)(H,63,91)(H,64,79)(H,65,87)(H,66,84)(H,67,88)(H,68,86)(H,69,82)(H,70,83)(H,71,85)(H,72,89)(H,73,90)(H,80,81)(H,94,95)/t26-,27+,32-,33-,34-,35-,36-,37-,38-,39-,40-,41-,42-,46-/m0/s1
InChI Key KXGCNMMJRFDFNR-WDRJZQOASA-N
No information available.
Summary of Clinical Use Click here for help
Used to treat chronic constipation and irritable bowel syndrome (IBS) where constipation is the main symptom (IBS-C).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Linaclotide mimics the action of heat-stable enterotoxins in the gut which would cause diarrhea via activation of the enzyme guanylate cyclase 2C (GUCY2C) [1]. Linaclotide activation of guanylate cyclase 2C in the luminal aspect of intestinal epithelium causes increased cGMP levels and this causes activation of the cystic fibrosis transmembrane conductance regulator (CFTR), which controls chloride ion efflux from enterocytes lining the GI tract. The result is a net efflux of water into the intestinal lumen which softens stools and stimulates bowel movements [2,4].
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)