Linaclotide

Linaclotide
Linaclotide structure. A 2D line-angle schematic of linaclotide (sequence CCEYCCNPACTGCY).[1] The phenolic ring of terminal tyrosine (Y) is in the lower left corner. Exaggerated bond lengths emphasize 3 disulfide (-S—S-) bonds between 6 cysteines (C's).
Clinical data
Trade namesLinzess
AHFS/Drugs.comMonograph
MedlinePlusa613007
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
  • L-Cysteinyl-L-cysteinyl-L-glutamyl-L-tyrosyl-L-cysteinyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-L-tyrosine cyclo(1-6),(2-10),(5-13)-tris(disulfide)
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.243.239 Edit this at Wikidata
Chemical and physical data
FormulaC59H79N15O21S6
Molar mass1526.73 g·mol−1
3D model (JSmol)
  • O=C(O)[C@@H](NC(=O)[C@H]4NC(=O)CNC(=O)[C@@H](NC(=O)[C@H]2NC(=O)[C@@H](NC(=O)[C@H]5N(C(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CSSC1)CSSC2)CCC(=O)O)Cc3ccc(O)cc3)CSSC4)CC(=O)N)CCC5)C)[C@H](O)C)Cc6ccc(O)cc6
  • 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 ☒N
  • Key:KXGCNMMJRFDFNR-WDRJZQOASA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Linaclotide, (sold under the brand name Linzess in the US and Mexico, and as Constella elsewhere)[6] is a drug used to treat irritable bowel syndrome with constipation and chronic constipation with no known cause.[4][3] It has a black box warning about the risk of serious dehydration in children in the US; the most common adverse effects in others include diarrhea.[4]

It is an oligopeptide agonist of guanylate cyclase 2C and remains in the GI tract after it is taken by mouth. It was approved in the US and the European Union in 2012.[7]

It is marketed by Abbvie (formerly Allergan) in the United states and by Astellas in Asia;[citation needed] Ironwood Pharmaceuticals was the originator.[8][failed verification] In 2021, it was the 246th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[9][10]

  1. ^ Oh SA (17 August 2011). "Macrocycle Milestone for Ironwood Pharma". The Haystack. Archived from the original on 27 November 2018. Retrieved 11 February 2017 – via CENBlog.org.
  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  3. ^ a b "UK label: Linaclotide Summary of Product Characteristics". Electronic Medicines Compendium. September 2017. Archived from the original on 15 April 2018. Retrieved 15 April 2018.
  4. ^ a b c "Linzess- linaclotide capsule, gelatin coated". DailyMed. 31 August 2021. Archived from the original on 29 March 2021. Retrieved 12 June 2023.
  5. ^ "Constella EPAR". European Medicines Agency. 24 May 2023. Archived from the original on 22 June 2021. Retrieved 12 June 2023.
  6. ^ "Linaclotide - Ironwood Pharmaceuticals". AdisInsight. Archived from the original on 7 October 2017. Retrieved 15 April 2018.
  7. ^ Yu SW, Rao SS (September 2014). "Advances in the management of constipation-predominant irritable bowel syndrome: the role of linaclotide". Therapeutic Advances in Gastroenterology. 7 (5): 193–205. doi:10.1177/1756283X14537882. PMC 4107700. PMID 25177366.
  8. ^ Nocera J (9 January 2018). "How Allergan Continues to Make Drug Prices Insane". Bloomberg News. Archived from the original on 15 April 2018. Retrieved 15 April 2018.
  9. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  10. ^ "Linaclotide - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.