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具有疗效的订书钉状、长效胰高血糖素样肽 2 类似物在葡聚糖硫酸钠诱导的小鼠结肠炎模型中的应用。

Stapled, Long-Acting Glucagon-like Peptide 2 Analog with Efficacy in Dextran Sodium Sulfate Induced Mouse Colitis Models.

机构信息

California Institute for Biomedical Research , La Jolla , California 92037 , United States.

Department of Chemistry, The Skaggs Institute for Chemical Biology , The Scripps Research Institute , La Jolla , California 92037 , United States.

出版信息

J Med Chem. 2018 Apr 12;61(7):3218-3223. doi: 10.1021/acs.jmedchem.7b00768. Epub 2018 Mar 23.

Abstract

Glucagon-like peptide 2 (GLP-2) is a hormone that has been shown to stimulate intestinal growth and attenuate intestinal inflammation. Despite being efficacious in a variety of animal models of disease, its therapeutic potential is hampered by the short half-life in vivo. We now describe a highly potent, stapled long-acting GLP-2 analog, peptide 10, that has a more than 10-fold longer half-life than teduglutide and improved intestinotrophic and anti-inflammatory effects in mouse models of DSS-induced colitis.

摘要

胰高血糖素样肽 2(GLP-2)是一种激素,已被证明可刺激肠道生长并减轻肠道炎症。尽管在多种疾病的动物模型中均有效,但由于其体内半衰期短,其治疗潜力受到限制。我们现在描述了一种高效、订书钉式长效 GLP-2 类似物,即肽 10,其半衰期比 teduglutide 长 10 多倍,并且在 DSS 诱导的结肠炎小鼠模型中具有更好的肠营养和抗炎作用。

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