中国药理学通报2017，Vol.33Issue(3)：321-326,6.DOI:10.3969/j.issn.1001-1978.2017.03.007
自噬相关蛋白ATG4 B抑制剂的虚拟筛选及体外活性测定
Virtual screening and in vitro activity studies of novel ATG4B inhibitors
摘要
Abstract
Aim ToscreenoutnovelATG4Binhibitors based on the computer-aided drug screening and inves-tigate the in vitro activities of these inhibitors.Methods Byperforminginsilicodockingbasedonthecrystal structure of ATG4B(PDB ID:2CY7),the SPECS da-tabase with 200000 compounds were screened.The inhibitory effect on ATG4B of those candidate com-pounds was verified by fluorescence resonance energy transferassay(FRET).Results Site5ofthe2CY7 was the most suitable pocket for molecular docking. After screening,30 compounds were purchased fromSPECS database for further bioassay.Among them, AG-690/10400046 effectively inhibited ATG4B activity invitrowithhighspecificity.Conclusion Apromising method is established for screening ATG4B inhibitors. Compound AG-690/10400046 is screened out with high activity and specificity.This work lays a founda-tion for virtual screening and later physiological func-tion studies of ATG4B inhibitors.关键词
ATG4B/抑制剂/分子对接/虚拟筛选/自噬/活性口袋5Key words
ATG4B/inhibitors/molecular docking/virtual screening/autophagy/pocket site 5分类
医药卫生引用本文复制引用
伏园园,吴一诺,喻秀,郭讷,张仁伟,刘翠,郑雪萍,戴琪,刘培庆..自噬相关蛋白ATG4 B抑制剂的虚拟筛选及体外活性测定[J].中国药理学通报,2017,33(3):321-326,6.基金项目
国家自然科学基金资助项目(No 31671437) （No 31671437）
广东省自然科学基金资助项目(No 2016A030313335) （No 2016A030313335）
