164757
CAS Number
851199-59-2Grade
Highly PurifiedMolecular Formula
C₅₉H₇₉N₁₅O₂₁S₆Molecular Weight
1526.74EU Commodity Code
38220090Shipping Temp
RTStorage Temp
-20°CLinaclotide
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)
Linaclotide is a peptide agonist of the guanylate cyclase C receptor (Ki = 16.4nM in a radioligand binding assay using mouse intestinal mucosa).1 Luminal exposure to 5ug of linaclotide stimulates fluid secretion and cGMP concentration in jejunal loops isolated from wild-type mice but not guanylate cyclase C receptor null mice. Linaclotide (100ug/kg) increases intestinal transit in wild-type mice. It also reduces the number of phosphorylated ERK-positive dorsal horn neurons in the thoracolumbar spinal cord, a marker of nociceptive signaling, following noxious colorectal distension and mechanical hypersensitivity in a mouse model of TNBS-induced colitis.2 Formulations containing linaclotide have been used for the treatment of constipation and pain associated with irritable bowel syndrome.
Synonyms
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)
Molecular Formula
C₅₉H₇₉N₁₅O₂₁S₆
Melting Point
>249 (dec) (lit)
Solubility
DMSO (Slightly), Water (Very Slightly)
Storage and Stability
Lyophilized product is stable for 6 months after receipt at -20°C. Reconstituted product is stable for 24 hours. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer. Hygroscopic. Store under inert atmosphere.
Important Note
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications without the expressed written authorization of United States Biological.
Toxicity and Hazards
All products should be handled by qualified personnel only, trained in laboratory procedures.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.
References
1. Bryant, A.P., Busby, R.W., Bartolini, W.P., et al. Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract Life Sci. 86(19-20):760-765 (2010). 2. Castro, J., Harrington, A.M., Hughes, P.A., et al. Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic guanosine 3',5'-monophosphate Gastroenterology 145(6):1334-1346 (2013). 3. Chey, W.D., et al.: Am. J. Gastroenterol., 107:1702 (2012) 4. Rao, S., et al.: Am. J. Gastroentrol., 107:1714 (2012) 5. Brierley, S.M., et al.: Curr. Opinion. Pharmacol., 12:632 (2012)USBio References
No references available