Virtual screening and high-throughput testing of L1 metallo-β-lactamase inhibitor

作     者：Chennan Liu Qian Wang Jiangxue Han Sihan Liu Chunling Xiao Yan Guan Xinghua Li Ying Wang Xiao Wang Jianzhou Meng Maoluo Gan Yishuang Liu 刘琛楠;王倩;韩江雪;刘思含;肖春玲;关艳;李兴华;王颖;王潇;蒙建州;甘茂罗;刘忆霜

作者机构：National Key Laboratory for Screening New Microbial DrugsInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2021年第30卷第10期

页      面：806-812页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：Natural Sciences Foundation of China (Grant No. 81872913) National High-tech R&D Program (863 Program, Grant No. 2015AA020911) 

主　　题：L1 Metallo-beta-lactamase inhibitor Virtual screening High-throughput screening 

摘      要：As a zinc-dependent enzyme, metal-β-lactamase L1 contributes to the development of β-lactam antibiotic resistance. The metal-β-lactamase inhibitor can restore the efficacy of β-lactam antibiotics, and its development has attracted much attention. In the present study, we used four widely-used virtual screening programs to screen 7035 small molecules to identify potential L1 inhibitors, and a high-throughput experimental model of L1 inhibitors was established. In this high-throughput testing model, the inhibition rate of 163 compounds on L1 exceeded 40%. The results of virtual screening of 7035 small molecules using the following four programs showed that among the top 1.35% of the compounds, their hit rates were ranked as Schr?dinger’s(5.26%), DS(1.05%), and Sybyl-x 2.0(1.05%), and Smina(2.11%).