| 基于药物重定位建立以α1酸性糖蛋白为靶点的高通量筛选平台及潜在减肥药物的发现 |
| 投稿时间：2023-09-25 修订日期：2024-02-04 点此下载全文 |
| 引用本文：陈枫,杨慈荣,张圳,陈飞,刘霞.基于药物重定位建立以α1酸性糖蛋白为靶点的高通量筛选平台及潜在减肥药物的发现[J].药学实践杂志,2024,42(3):114~120 |
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| 中文摘要:目的 α1酸性糖蛋白（ORM）是减肥药物研发的新靶点。基于药物重定位，拟从已上市药物的化合物库中寻找可以靶向ORM的潜在减肥药物。方法 构建pGL4.20-ORM1 启动子重组质粒，验证后利用慢病毒载体构建稳定表达ORM1 启动子-LUC-PURO的AML12细胞株，利用该细胞株对上市药物库中化合物进行高通量筛选，通过酶标仪对细胞的荧光值进行表征。结果 对1 470种化合物进行初筛和复筛，发现42种化合物可以提高ORM1启动子表达，可用于进一步的减肥效应评估。结论 通过慢病毒载体成功构建了LV-AML12-ORM1 启动子-LUC-PURO稳定表达细胞株，为高效、稳定筛选靶向ORM的减肥药物奠定了基础。 |
| 中文关键词:药物重定位 α1酸性糖蛋白 高通量筛选 肥胖 减肥药物 |
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| Establishment of a high-throughput screening platform based on drug repurposing targeting alpha-1-acid glycoprotein and discovery of potential weight loss drugs |
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| Abstract:Objective Alpha-1-acid glycoprotein （ORM） was a new target for the development of weight loss drugs. To search for potential weight loss drugs that could target ORM from the compound library of already marketed drugs based on drug repurposing. Methods The pGL4.20-ORM1 promoter recombinant plasmid was contructed and validated, and then a lentiviral vector was utilized to establish stable AML12 cell lines expressing ORM1 promoter-LUC-PURO. This cell line was employed for high-throughput screening of compounds from the marketed drug library, and the luminescence value of the cells was characterized by enzyme marker. Results Primary screening and secondary screening of 1 470 compounds identified 42 compounds that increased ORM1 promoter expression and could be used for further weight loss effect assessment. Conclusion This study successfully constructed LV-AML12-ORM1 promoter-LUC-PURO stable expression cell lines using lentiviral vectors, laying a foundation for efficient and stable screening of weight loss drugs targeting ORM. |
| keywords:drug repurposing ORM high-throughput screening obesity weight loss drugs |
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