Linaclotide

Modify Date: 2024-01-02 14:56:00

Linaclotide structure	Common Name	Linaclotide
	CAS Number	851199-59-2	Molecular Weight	1526.736
	Density	1.6±0.1 g/cm3	Boiling Point	2045.0±65.0 °C at 760 mmHg
	Molecular Formula	C₅₉H₇₉N₁₅O₂₁S₆	Melting Point	N/A
	MSDS	N/A	Flash Point	1190.5±34.3 °C

Use of Linaclotide

Linaclotide is a potent and selective guanylate cyclase C agonist; developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic constipation.

Name	linaclotide
Synonym	More Synonyms

Description	Linaclotide is a potent and selective guanylate cyclase C agonist; developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic constipation.
Related Catalog	Signaling Pathways >> GPCR/G Protein >> Guanylate Cyclase Research Areas >> Others
In Vitro	Linaclotide inhibits in vitro [125I]-STa binding to intestinal mucosal membranes from wt mice in a concentration-dependent manner. In contrast, [125I]-STa binding to these membranes from GC-C null mice is significantly decreased. After incubation in vitro in jejunal fluid for 30 min, linaclotide is completely degraded[1]. Linaclotide acts on guanylate cyclase-C receptors on the luminal membrane to increase chloride and bicarbonate secretions into the intestine and inhibit the absorption of sodium ions, thus increasing the secretion of water into the lumen and improving defecation; the drug is minimally absorbed into the systemic circulation[2].
In Vivo	Pharmacokinetic analysis shows very low oral bioavailability (0.10%). In intestinal secretion and transit models, linaclotide exhibits significant pharmacological effects in wt, but not in GC-C null mice: induction of increased fluid secretion into surgically ligated jejunal loops is accompanied by the secretion of elevated levels of cyclic guanosine-3',5-monophosphate and accelerated gastrointestinal transit[1]. Linaclotide significantly increases weekly spontaneous bowel movements and complete spontaneous bowel movements (CSBMs) while reducing abdominal pain in patients with chronic constipation[2].
Animal Admin	Mice: To determine oral bioavailability, three groups (n=3) of female CD-1 mice receive linaclotide (8 mg/kg) intravenously (i.v.), while two groups (n=3) receive linaclotide (8 mg/kg) by gavage (p.o.). Blood is allowed to clot for 5 min, centrifuged at 13,000×g for 3 min, and the serum is collected and stored at −80 °C until sample preparation and analysis by LC-MS/MS[1].
References	[1]. Bryant AP, et al. Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. Life Sci. 2010 May 8;86(19-20):760-5. [2]. Love BL, et al. Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome. Am J Health Syst Pharm. 2014 Jul 1;71(13):1081-91.

Density	1.6±0.1 g/cm3
Boiling Point	2045.0±65.0 °C at 760 mmHg
Molecular Formula	C₅₉H₇₉N₁₅O₂₁S₆
Molecular Weight	1526.736
Flash Point	1190.5±34.3 °C
Exact Mass	1525.389893
PSA	725.71000
LogP	-5.84
Vapour Pressure	0.0±0.3 mmHg at 25°C
Index of Refraction	1.712

Linzess

Linaelotide Acetate

L-Tyrosine, L-cysteinyl-L-cysteinyl-L-α-glutamyl-L-tyrosyl-L-cysteinyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-, cyclic (1→6),(2→10),(5→13)-tris(disulfide)

L-cysteinyl-L-cysteinyl-L-α-glutamyl-L-tyrosyl-L-cysteinyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-L-tyrosine cyclic (1->6),(2->10),(5->13)-tris(disulfide)

Constella

Linaclotide

LINACLOTIDE ACETATE

Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (disulfide bridge: 1-6; 2-10; 5-13)

N-({(1R,4S,7S,13S,16R,21R,24R,27S,30S,33R,38R,44S)-21-Amino-13-(2-amino-2-oxoethyl)-27-(2-carboxyethyl)-30-(4-hydroxybenzyl)-44-[(1R)-1-hydroxyethyl]-4-methyl-3,6,12,15,22,25,28,31,40,43,46,51-dodecao ;xo-18,19,35,36,48,49-hexathia-2,5,11,14,23,26,29,32,39,42,45,52-dodecaazatetracyclo[22.22.4.2.0]dopentacont-38-yl}carbonyl)-L-tyrosine