Лираглутид

Химические свойства

Liraglutide is characterized as a white to almost white powder. It is freely soluble in aqueous base solutions (> 270 mg/mL), but its water solubility decreases below pH 7 and reaches its lowest level at pH 4-5 (approximately 0.05 mg/mL). Solubility increases marginally at pH 2.5 where it is very slightly soluble (≤ 0.8 mg/mL). Liraglutide is soluble in methanol (68 mg/mL) and very slightly soluble in ethanol (1.1 mg/mL). The isoelectric point of liraglutide is approximately 4.9. The pH of a 1 mg/mL aqueous solution of drug substance is approximately 9.3.

Использование

Liraglutide is a new type of hypoglycemic drug that activates AMP-activated protein kinase thus enhancing insulin sensitivity. It not only has a significant hypoglycemic effect, but also has the functions of weight loss, blood pressure reduction, and improvement of blood lipid profile.
Liraglutide, a human glucagon-like peptide-1 (GLP-1) receptor agonist, slows gastric emptying, increases satiety, and reduces patient eating, while reducing the brain's desire to eat and allowing the body to Increased energy expenditure plays a role in weight loss; it prevents the liver from producing too much glucose and promotes the pancreas to produce more insulin to lower blood sugar; in addition, liraglutide also has cardiovascular benefits and kidney protection.

Определение

ChEBI: Liraglutide, a lipopeptide and polypeptide, is an analogue of human GLP-1 in which the lysine residue at position 27 is replaced by arginine and a hexadecanoyl group attached to the remaining lysine via a glutamic acid spacer. It is used alongside diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Liraglutide functions as a glucagon-like peptide-1 receptor agonist and serves as a neuroprotective agent.

Общее описание

Liraglutide is GLP-1(1–37) modified at Ly: the -amino group is acylated with an (N-hexadecanoyl)glutam- -yl moiety that noncovalently but avidly binds tohuman serum albumin. (Also, Lys is conservatively replacedwith Arg.) These changes provide for a greatly extendedserum t1?2 of～10 to 15 hours after sc administration(0.6–1.8 mg), allowing for once-daily dosing.Liraglutide (Victoza, Novo Nordisk) is awaiting approvalby the FDA, EMEA, and the Koˉ roˉ -shoˉ (Japan).

Биологическая активность

Liraglutide is a highly potent, long-acting GLP-1 receptor agonist (EC50 = 61 pM). Acylated derivative of GLP-1 (7-37) (Cat. No. 5374). Inhibits food and water intake, causing lasting and reversible weight loss in normal and obese rats. In an animal model of Alzheimer's disease, Liraglutide decreases levels of Aβ and soluble amyloid, and reduces neuroinflammation.

Побочные эффекты

The most frequent adverse events associated with liraglutide therapy were gastrointestinal in nature, in accordance with GLP-1 receptor activation, and included nausea, diarrhea, vomiting, constipation, abdominal pain, and dyspepsia.

Способ действия

Liraglutide is an acylated human glucagon-like peptide-1 (GLP-1) receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). Like endogenous GLP-1, liraglutide binds to and activates the GLP-1 receptor, a cellsurface receptor coupled to adenylyl cyclase activation through the stimulatory G-protein, Gs. Endogenous GLP-1 has a half-life of 1.5-2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase 4 (DPP-4) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration.