人β3肾上腺素受体激动剂快速筛选模型的建立

Construction of Drug Screening Model for Human β-3 Adrenergic Receptor Agonists

目的:β3肾上腺素受体(beta-3 adrenergic receptor,ADRB3)是β肾上腺素受体的一个亚型,是一个公认的减肥药和抗2型糖尿病药物研发的重要分子靶点,构建其激动剂筛选模型具有重要意义。方法:以ADRB3发挥作用的细胞内信号通路为理论依据,在细胞水平上构建了以荧光素酶为报告基因的人ADRB3激动剂药物筛选模型,并对部分实验条件进行了快速简易优化。结果:已知的ADRB3激动剂异丙肾上腺素和倍他福林均能够有效激活该筛选模型中pCRE-luc报告基因质粒的表达,使其表达增加3倍以上。结论:该筛选模型构建成功。目前该模型已用于以ADRB3为靶点减肥新药筛选。

Objective：As human β-3 adrenergic receptor（ADRB3）,a subtype of beta adrenergic receptor,is a well-known molecular target for anti-obesity and anti-diabeties type Ⅱ drug development,constructing its agonist screening model is of importance.Method：Based on literature search and our previous work,a luciferase-based drug screening model for human ADRB3 agonists was constructed in the present study.The model was also optimized in several aspects of experimental condition.Result：Finally,the known ADRB3 agonists such as isoprenaline and betaphrine significantly activated the expression of pCRE-luc reporter.Conclusion：The screening model was constructed succesfully.Currently,the model has been used for screening novel human ADRB3 agonists.