Home GPCR & G Protein Glucagon Receptor agonist Lixisenatide

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Lixisenatide Glucagon Receptor agonist

Cat.No.S8517

Lixisenatide (Lyxumia, Adlyxin, ZP10A peptide, AVE0010) 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.
Lixisenatide Glucagon Receptor agonist Chemical Structure

Chemical Structure

Molecular Weight: 4858.49

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Chemical Information, Storage & Stability

Molecular Weight 4858.49 Formula

C215H347N61O65S

 Storage (From the date of receipt)
CAS No. 320367-13-3 Download SDF Storage of Stock Solutions

Synonyms Lyxumia, Adlyxin, ZP10A peptide, AVE0010 Smiles CCC(C)C(C(=O)NC(CCC(=O)O)C(=O)NC(CC1=CNC2=CC=CC=C21)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(=O)N)C(=O)NCC(=O)NCC(=O)N3CCCC3C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N4CCCC4C(=O)N5CCCC5C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)N)NC(=O)C(CC6=CC=CC=C6)NC(=O)C(CC(C)C)NC(=O)C(CCCNC(=N)N)NC(=O)C(C(C)C)NC(=O)C(C)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCSC)NC(=O)C(CCC(=O)N)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CC7=CC=CC=C7)NC(=O)C(C(C)O)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)CNC(=O)C(CC8=CNC=N8)N

Solubility

In vitro
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Water : 100 mg/mL

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In vivo
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Mechanism of Action

Targets/IC50/Ki
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, this compound 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 it is a very potent and selective GLP-1 receptor agonist--the binding affinity of this chemical (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, it 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. This compound can significantly improve glucose-stimulated insulin secretion. In healthy normoglycemic dogs, single subcutaneous injections of this agent 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 this peptide 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 administration of this compound 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 this agent 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. This chemical can maintain beta cell mass and function through stimulation of islet cell proliferation and neogenesis, and inhibition of islet cell apoptosis[1]. It preserves pancreatic responsiveness in diabetic animals[3].
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02274740 Terminated
Type II Diabetes Mellitus
Sanofi
 April 2015 Phase 2

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