Constella

Linaclotide

Linaclotide structure. A 2D line-angle schematic of linaclotide (sequence CCEYCCNPACTGCY). 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 names	Linzess
License data	US FDA: Linaclotide
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Oral
ATC code	A06AX04 (WHO)
Legal status
Legal status	US: ℞-only
Identifiers
IUPAC name 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	851199-59-2 Y
PubChem CID	16158208
IUPHAR/BPS	5017
ChemSpider	17314504 N
UNII	N0TXR0XR5X
KEGG	D09355 Y
Chemical and physical data
Formula	C59H79N15O21S6
Molar mass	1526.74 g/mol
3D model (JSmol)	Interactive image
SMILES 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 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
NY (what is this?)

Linaclotide (marketed under the trade name Linzess in the US and Mexico, and as Constella in Canada and many other countries) is an oligo-peptide agonist of guanylate cyclase 2C. It was approved by the FDA in August 2012 and by the European Medicines Agency for the treatment in adults of constipation-predominant irritable bowel syndrome and chronic idiopathic constipation.

The National Institutes of Health (NIH) estimate that as many as 20% of Americans may experience irritable bowel syndrome (IBS); approximately one-third of those, as many as 10 million Americans, experience constipation-predominant IBS (IBS-C), that is, IBS with constipation often accompanied by abdominal pain.Laxatives can assist with constipation but do not treat pain, while opiates that are often prescribed to treat pain can aggravate constipation. While low-cost laxatives and pain killers would likely be tried first, linaclotide targets both associated conditions in a once-daily pill.

Linaclotide is a peptide mimic of endogenous guanylin and uroguanylin. It is a synthetic tetradecapeptide (14 amino acid peptide) with the sequence CCEYCCNPACTGCY by one-letter abbreviation, or by three-letter abbreviation:

H–Cys¹–Cys²–Glu³–Tyr⁴–Cys⁵–Cys⁶–Asn⁷–Pro⁸–Ala⁹–Cys¹⁰–Thr¹¹–Gly¹²–Cys¹³–Tyr¹⁴–OH