Glucagon-Like Peptide-1 Receptor Agonists and Strategies To Improve Their Efficiency,Molecular Pharmaceutics

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Glucagon-Like Peptide-1 Receptor Agonists and Strategies To Improve Their Efficiency
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2019-05-03 00:00:00 , DOI: 10.1021/acs.molpharmaceut.9b00308
Seyed Ebrahim Alavi ₁ , Peter J. Cabot ₁ , Peter M. Moyle ₁

Affiliation

Type 2 diabetes mellitus (T2DM) is increasing in global prevalence and is associated with serious health problems (e.g., cardiovascular disease). Various treatment options are available for T2DM, including the incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1 is a therapeutic peptide secreted from the intestines following food intake, which stimulates the secretion of insulin from the pancreas. The native GLP-1 has a very short plasma half-life, owning to renal clearance and degradation by the enzyme dipeptidyl peptidase-4. To overcome this issue, various GLP-1 agonists with increased resistance to proteolytic degradation and reduced renal clearance have been developed, with several currently marketed. Strategies, such as controlled release delivery systems, methods to reduce renal clearance (e.g., PEGylation and conjugation to antibodies), and methods to improve proteolytic stability (e.g., stapling, cyclization, and glycosylation) provide means to further improve the ability of GLP-1 analogs. These will be discussed in this literature review.

中文翻译：

胰高血糖素样肽1受体激动剂和提高其效率的策略

2型糖尿病（T2DM）的全球患病率正在上升，并且与严重的健康问题（例如，心血管疾病）相关。T2DM有多种治疗选择，包括肠降血糖素激素胰高血糖素样肽1（GLP-1）。GLP-1是一种在食物摄入后从肠道分泌的治疗性肽，可刺激胰腺分泌胰岛素。天然的GLP-1具有非常短的血浆半衰期，归因于肾脏清除和二肽基肽酶-4酶的降解。为了克服这个问题，已经开发了对蛋白水解降解具有增强的抵抗力和降低的肾清除率的各种GLP-1激动剂，其中几种目前已经上市。策略，例如控释递送系统，降低肾脏清除率的方法（例如，聚乙二醇化和与抗体结合），改善蛋白水解稳定性的方法和方法（例如装订，环化和糖基化）提供了进一步提高GLP-1类似物能力的方法。这些将在本文献综述中讨论。

更新日期：2019-05-03

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