Constella™(EU)-Linzess™(USA): the last milestone in the long journey of the peptide linaclotide and its implications for the future of peptide drugs

Future Med Chem. 2013 Mar;5(3):291-300. doi: 10.4155/fmc.13.5.

Abstract

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are highly prevalent gastrointestinal disorders associated with health, economical and social problems. Recently, after a long journey of preclinical studies and clinical trials, linaclotide, a first-in-class GC-C receptor peptide agonist, has received the approval in the USA and Europe for the treatment of IBS-C and CIC. This article provides an overview of clinical, economic and biological aspects of IBS-C and CIC and covers the current and emerging therapeutic agents for treating these conditions. Particularly, the pharmacodynamic and pharmacokinetic properties of linaclotide, a small, disulfide-rich peptide, and its implications in the future of peptide drug discovery and development are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chronic Disease
  • Colon / pathology
  • Constipation / complications*
  • Constipation / drug therapy*
  • Constipation / economics
  • Constipation / pathology
  • Humans
  • Irritable Bowel Syndrome / complications*
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / economics
  • Irritable Bowel Syndrome / pathology
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / pharmacokinetics
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled / agonists*
  • Receptors, Guanylate Cyclase-Coupled / metabolism
  • Receptors, Peptide / agonists*
  • Receptors, Peptide / metabolism

Substances

  • Peptides
  • Receptors, Peptide
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled
  • linaclotide