Abstract：
Glucagon-like peptide-1 receptor (GLP-1R) is a pivotal receptor involved in blood glucose regulation and influencing feeding behavior. It has received significant attention in the treatment of obesity and diabetes due to its potent incretin effect. Peptide GLP-1 receptor agonists (GLP-1RAs) have achieved tremendous success in the market, driving the vigorous development of small molecule GLP-1RAs. Currently, several small molecules have entered the clinical research stage. Additionally, recent discoveries of GLP-1R positive allosteric modulators (PAMs) are also unveiling new regulatory patterns and treatment methods. This article reviews the structure and functional mechanisms of GLP-1R, recent reports on small molecule GLP-1RAs and PAMs, as well as the optimization process. Furthermore, it combines computer simulations to analyze structure-activity relationships (SAR) studies, providing a foundation for exploring new strategies for designing small molecule GLP-1RAs.
摘要：
胰高血糖素样肽-1受体（GLP-1R）是参与血糖调节和影响摄食行为的关键受体。由于其有效的肠促胰岛素作用，它在肥胖和糖尿病的治疗中受到了极大的关注。肽类GLP-1受体激动剂（GLP-1RAs）在市场上取得了巨大的成功，推动小分子GLP-1RAs的蓬勃发展。目前,一些小分子已经进入临床研究阶段。此外,GLP-1R正变构调节剂（PAMs）的最新发现也揭示了新的调控模式和治疗方法。本文综述了GLP-1R的结构和功能机制。最近关于小分子GLP-1RA和PAMs的报道，以及优化过程。此外，它结合了计算机模拟来分析结构-活动关系(SAR)研究，为探索设计小分子GLP-1RAs的新策略奠定了基础。
