Lixisenatide

Catalog No.S8517 Synonyms: Lyxumia, Adlyxin, ZP10A peptide, AVE0010

Lixisenatide Chemical Structure

Molecular Weight(MW): 4858.49

Lixisenatide is a once-daily short-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) with an IC50 of 1.4 nM for the human GLP-1 receptor in receptor binding studies.

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Biological Activity

Description Lixisenatide is a once-daily short-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) with an IC50 of 1.4 nM for the human GLP-1 receptor in receptor binding studies.
Targets
GLP-1R [1]
(Cell-free assay)
1.4 nM
In vitro

Lixisenatide protects Ins-1 cells (a rat-derived β-cell line) from both lipid- and cytokine-induced apoptosis. More importantly, Lixisenatide also prevents lipotoxicity-induced insulin depletion in human islets and preserves insulin production, storage and pancreatic β-cell function in vitro. Binding studies in CHO-K1 cells overexpressing the human GLP-1 receptor show that Lixisenatide is a very potent and selective GLP-1 receptor agonist--the binding affinity of Lixisenatide (Ki = 1.33 ± 0.22 nM) is ∼ 4-times greater than that of human GLP-1 (Ki = 5.09 ± 1.19 nM). In more than 80 different binding assays, lixisenatide does not exhibit any relevant interaction with other potential drug targets, confirming its high selectivity for the GLP-1 receptor[3].

In vivo The half-life of lixisenatide is 2-4 hours, and it is classed as a short-acting GLP-1-receptor agonist, compared with the long-acting GLP-1-based peptides, liraglutide and albiglutide. Lixisenatide can significantly improve glucose-stimulated insulin secretion. In healthy normoglycemic dogs, single subcutaneous injections of lixisenatide produces dose-dependent reductions in plasma glucose after an oral glucose challenge and significantly reduces postprandial glucose excursions by 67% compared with placebo without increasing insulin concentrations. The effect of lixisenatide on postprandial blood glucose excursions in dogs is, at least in part, related to inhibition of gastric emptying and delayed intestinal glucose absorption. Dose-dependent reductions in plasma glucose after an oral glucose challenge have also been demonstrated in both the db/db mouse and ZDF rat. Importantly, this activity is glucose-dependent with no effect at physiological glucose concentrations. In db/db mice, chronic lixisenatide administration preventes the progressive deterioration in glucose tolerance observed in control animals and is associated with significant dose-dependent reductions in glycosylated hemoglobin (HbA1c). In ZDF rats, a continuous subcutaneous infusion of lixisenatide 50 μg/kg/day for 12 weeks significantly decreases basal blood glucose and improves oral glucose tolerance compared with control animals. It has no hypoglycemic effect and does not change HbA1c in normoglycemic rats. Lixisenatide can maintain beta cell mass and function through stimulation of islet cell proliferation and neogenesis, and inhibition of islet cell apoptosis[1]. Lixisenatide preserves pancreatic responsiveness in diabetic animals[3].

Protocol

Animal Research:

[2]

+ Expand
  • Animal Models: Male db/db mice C57BLKS/J-Leprdb/Leprdb
  • Formulation: phosphate-buffered saline, pH 7.4
  • Dosages: 0.01, 0.1, 1, 10, and 100 nmol/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro Water 100 mg/mL (20.58 mM)

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 4858.49
Formula

C215H347N61O65S

CAS No. 320367-13-3
Storage powder
in solvent
Synonyms Lyxumia, Adlyxin, ZP10A peptide, AVE0010

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02274740 Terminated Drug: LIXISENATIDE AVE0010|Drug: metformin Type II Diabetes Mellitus Sanofi April 2015 Phase 2

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID