Drug discovery approaches targeting the incretin pathway.,Bioorganic Chemistry

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Drug discovery approaches targeting the incretin pathway.
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2020-04-02 , DOI: 10.1016/j.bioorg.2020.103810
Xinxian Deng ₁ , Mojdeh S Tavallaie ₁ , Ran Sun ₁ , Juntao Wang ₁ , Qingqing Cai ₂ , Jian Shen ₃ , Shuwen Lei ₁ , Lei Fu ₁ , Faqin Jiang ₁

Affiliation

Incretin pathway plays an important role in the development of diabetes medications. Interventions in DPP-4 and GLP-1 receptor have shown remarkable efficacy in experimental and clinical studies and imperatively become one of the most promising therapeutic approaches in the T2DM drug discovery pipeline. Herein, we analyzed the actionmechanismsof DPP-4 and GLP-1 receptor targeting the incretin pathway in T2DM treatment. We gave an insight into the structural requirements for the potent DPP-4 inhibitors and revealed a classification of DPP-4 inhibitors by stressing on the binding modes of these ligands to the enzyme. We then reviewed the drug discovery strategies for the development of peptide and non-peptide GLP-1 receptor agonists (GLP-1 RAs). Furthermore, the drug design strategies for DPP-4 inhibitors and GLP-1R agonists were detailed accurately. This review might provide an efficient evidence for the highly potent and selective DPP-4 inhibitors and the GLP-1 RAs, as novel medicines for patients suffering from T2DM.

中文翻译：

针对肠降血糖素途径的药物发现方法。

Incretin途径在糖尿病药物的开发中起重要作用。在实验和临床研究中，对DPP-4和GLP-1受体的干预已显示出显着的功效，并势必成为T2DM药物开发流程中最有希望的治疗方法之一。本文中，我们分析了在T2DM治疗中针对肠降血糖素途径的DPP-4和GLP-1受体的作用机理。我们深入了解了强效DPP-4抑制剂的结构要求，并通过强调这些配体与酶的结合方式揭示了DPP-4抑制剂的分类。然后，我们回顾了用于肽和非肽GLP-1受体激动剂（GLP-1 RA）开发的药物发现策略。此外，准确地详细介绍了DPP-4抑制剂和GLP-1R激动剂的药物设计策略。

更新日期：2020-04-20

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