Specialized Research FDA Approved

Linaclotide

Also known as: Linzess, Constella, Linaclotida

Molecular Identifiers

Molecular Formula

C59H79N15O21S6

CAS Number

851199-59-2

PubChem CID

16158208

Molecular Weight

1526.8 Da

Overview

Guanylate cyclase-C (GC-C) receptor agonist peptide, composed of 14 amino acids with three disulfide bonds and a molecular weight of approximately 1,526.8 Da. Approved for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation. Acts locally in the intestine with minimal systemic absorption.

Approved by the FDA as Linzess (2012) for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults.

The main clinical interest around linaclotide is the control of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation: by activating the guanylate cyclase-C (GC-C) receptor on intestinal epithelial cells, it increases fluid secretion into the lumen and accelerates transit, while reducing visceral pain through the action of extracellular cGMP on afferent nerves. Unlike most peptides in this database, it is taken orally and acts predominantly locally, with minimal systemic absorption.

It was approved by the FDA in 2012 as Linzess (Ironwood/AbbVie) and is marketed in Europe as Constella. It is available at standard pharmacies with prescription, in doses of 72, 145, or 290 mcg once daily, 30 minutes before the first meal of the day. Diarrhea is the most common adverse effect, and the drug is contraindicated in children under 6 years.

Sequence (1 letter): CCEYCCNPACTGCY

Extended notation: Cys-Cys-Glu-Tyr-Cys-Cys-Asn-Pro-Ala-Cys-Thr-Gly-Cys-Tyr

Half-life

~3-5 minutes (local, intestinal)

Administration Route

Oral

Mechanism of Action

Activation of the guanylate cyclase-C (GC-C) receptor on intestinal epithelial cells
Increased intracellular cGMP (cyclic guanosine monophosphate) production
Stimulation of chloride and bicarbonate secretion into the intestinal lumen
Increased intestinal fluid secretion and acceleration of transit
Reduction of visceral pain via extracellular cGMP signaling on afferent nerves
Inhibition of visceral afferent nociceptors

Dosage Protocol

Data compiled from the literature. This does not constitute medical advice.

Parameter	Value
Dose	72-290 mcg oral (subcutaneous research 100-500 mcg)
Frequency	Once daily (oral)
Timing	30 minutes before the first meal of the day
Duration	Continuous use (oral) or 4-8 weeks (research)

Reported Side Effects

Adverse effects described in the literature. Severity and frequency vary between individuals.

Diarrhea
Abdominal pain
Flatulence
Abdominal distension

Product Properties

Purity	>95%
Appearance	White lyophilized powder
Solubility	Soluble in water and bacteriostatic water
Source	Solid-phase peptide synthesis (SPPS) with oxidative folding for disulfide bond formation
Storage	Lyophilized: -20°C for up to 2 years, 2-8°C for up to 6 months. Reconstituted: 2-8°C for up to 2 weeks. Contains 3 disulfide bonds critical for activity — avoid reducing conditions. Protect from light and moisture. Avoid repeated freeze-thaw cycles.

Presentations & Preparation

Vials of Linaclotide found in the research market:

5 mg10 mg

Reconstitution

Diluent: Bacteriostatic water (for research formulation)
Volume: 1-2 ml per vial
For oral use, administer intact capsules — do not open or chew
For subcutaneous research, reconstitute with sterile diluent
Gently swirl until completely dissolved — never shake

Storage

Lyophilized: Refrigerated 2-8°C (research); room temperature for commercial capsules
Reconstituted: Refrigerated 2-8°C (up to 14 days)
Protect from moisture (capsules)
Keep in original packaging until use
Do not freeze after reconstitution

Reconstitution Calculator