Investigational Drug Details
| Drug ID: | D476 |
| Drug Name: | Linaclotide |
| Synonyms: | |
| Type: | small molecule |
| DrugBank ID: | DB08890 |
| DrugBank Description: | Linaclotide is an orally administered, peptide agonist of guanylate cyclase 2C for the treatment of irritable bowel syndrome. Chemically, it is a heterodetic cyclic peptide and consists of fourteen amino acids. The protein sequence is as follows: Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr. There are three disulfide bonds which are located between Cys1 and Cys6; between Cys2 and Cys10; and between Cys5 and Cys13. FDA approved on August 30, 2012. |
| PubChem ID: | 16158208 |
| CasNo: | 851199-59-2 |
| Repositioning for NAFLD: | Yes |
| SMILES: | [H][C@]1(CSSC[C@]2([H])NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]3CSSC[C@H](NC(=O)[C@H](C)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CSSC[C@H](N)C(=O)N3)NC2=O)C(=O)N[C@@]([H])([C@@H](C)O)C(=O)NCC(=O)N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O |
| Structure: |
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| InChiKey: | KXGCNMMJRFDFNR-WDRJZQOASA-N |
| Molecular Weight: | 1526.736 |
| DrugBank Targets: | Heat-stable enterotoxin receptor |
| DrugBank MoA: | Linaclotide is an agonist of guanylate cyclase-C (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. 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. |
| DrugBank Pharmacology: | Changes in the appearance and consistency of stools as measured by the Bristol Stool Form Scale (BSFS) have been noted after taking linaclotide. |
| DrugBank Indication: | Treatment of irritable bowel syndrome (IBS) with constipation and chronic idiopathic constipation. |
| Targets: | |
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