Teduglutide Chemical Properties

solubility 

Methanol (Slightly), Water (Slightly)

form 

Solid

color 

White to Off-White

Stability:

Hygroscopic

InChIKey

CILIXQOJUNDIDU-ASQIGDHWSA-N

Safety Information

Hazardous Substances Data

197922-42-2(Hazardous Substances Data)

Teduglutide Usage And Synthesis

Description

Teduglutide was approved in August 2012 by the European Commission and in December 2012 by the US FDA for the treatment of adults with short bowel syndrome (SBS) who are dependent on parenteral nutrition (PN). Teduglutide (also known as ALX-0600) is a GLP-2 analogue in which glycine has been substituted for alanine at position 2 from the N-terminus, thereby conferring resistance to degradation by DPP-4. Teduglutide has similar binding affinity, agonist potency, and agonist efficacy as GLP-2 in assays with the rat GLP-2 receptor. Administration of teduglutide to rats gave a significant increase in small intestine weight and an increase in the height of intestinal villi. Teduglutide was prepared by solid-phase peptide synthesis.

Originator

NPS Allelix (Canada)

Uses

Treatment of intestinal diseases characterized by chemical or surgical damage of the intestinal epithelium such as Short Bowel Syndrome (SBS) or damage to the intestinal epithelium due to disease (glucagon-like peptide-2 (GLP- 2) analog).

Definition

ChEBI: A 33-membered polypeptide consisting of His, Gly, Asp, Gly, Ser, Phe, Ser, Asp, Glu, Met, Asn, Thr, Ile, Leu, Asp, Asn, Leu, Ala, Ala, Arg, Asp, Phe, Ile, Asn, Trp, Leu, Ile, Gln, Thr, Lys, Ile, Thr and Asp residues joined in sequence. A glucagon-like pep ide-2 receptor agonist used for the treatment of short-bowel syndrome.

Application

Teduglutide is a peptide hormone that is used to treat pediatric patients with long-term efficacy. It has been shown to be effective in the treatment of autoimmune diseases and bowel disease. It is a long-acting analogue of glucagon-like peptide 1 (GLP-1). The drug has been shown to have high chemical stability, which means it does not break down easily. Teduglutide is injected into the body and taken up by cells, where it activates receptors on the surface of cells. This activation leads to increased glucose production by the liver and improved insulin sensitivity in peripheral tissues such as muscle, fat, and liver. It also increases heart rate and blood pressure.

brand name

Gattex

Mechanism of action

Gattex (teduglutide) is an analog of naturally occurring human glucagon-like peptide 2 (GLP-2), a peptide secreted primarily in the distal intestine and involved in the regeneration and repair of the intestinal epithelium. GLP-2 is known to increase intestinal and portal blood flow, and inhibit gastric acid secretion.Teduglutide binds to the GLP-2 receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus. Activation of these receptors results in the local release of multiple mediators including insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF).

Clinical Use

Human glucagon-like peptide-2 (GLP-2):
Treatment of short bowel syndrome

Side effects

Side effects that you should report to your care team as soon as possible:
Allergic reactions—skin rash, itching, hives, swelling of the face, lips, tongue, or throat
Bowel blockage—stomach cramping, unable to have a bowel movement or pass gas, loss of appetite, vomiting
Gallbladder problems—severe stomach pain, nausea, vomiting, fever
Pancreatitis—severe stomach pain that spreads to your back or gets worse after eating or when touched, fever, nausea, vomiting

Drug interactions

Potentially hazardous interactions with other drugs
Potential for increased absorption of some medications. Monitor narrow therapeutic index drugs carefully.

Metabolism

The metabolism of teduglutide is not fully known. Since teduglutide is a peptide it is likely that it follows the principal mechanism for peptide metabolism. See 'Other information'.

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