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  

Establishment of a high-throughput screening platform based on drug repurposing targeting alpha-1-acid glycoprotein and discovery of potential weight loss drugs

作　　者：陈枫 杨慈荣 张圳 陈飞 刘霞 CHEN Feng;YANG Cirong;ZHANG Zhen;CHEN Fei;LIU Xia(School of Pharmacy,Naval Medical University,Shanghai 200433,China;Unit 92,92730 Force,Sanya 572000,China)

机构地区：[1]海军军医大学药学系临床药学教研室,上海200433 [2]92730部队92分队,海南三亚572000

出　　处：《药学实践与服务》2024年第3期114-120,共7页Journal of Pharmaceutical Practice and Service

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1470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。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 1470 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.

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 

分 类 号：R965.1[医药卫生—药理学]