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Discovery of Linaclotide

The diagram below illustrates the three dimensional structure of the linaclotide molecule.

3D structure of Linaclotide molecules containing T Y R14, C Y S13, C Y S5, C Y S1, C Y S6,C Y S10, C Y S2 and T Y R4 residues joined sequence and cyclized by three disulfide bonds between C Y S(1) and C Y S(6), C Y S(2) and C Y S(10), and C Y S(5) and C Y S(13).

Linaclotide was discovered as a result of Ironwood’s pioneering research on the intestinal enzyme guanylate cyclase-C (GC-C) and went on to become the first GC-C agonist approved in the U.S., establishing GC-C agonists as a new class of medicines.

GC-C is found mainly on the surface of the intestine and is thought to be a potential target for a variety of gastrointestinal diseases. Ironwood developed an orally available peptide – linaclotide – that selectively hits this target and can survive the harsh acidic environment of the stomach to reach GC-C in the intestine.

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