目的 从天然产物中发现新的去泛素化酶2 （USP2）抑制剂。方法 利用泛素荧光检测试剂盒进行USP2抑制剂筛选。100 μmol/L紫菀酮（SH）处理NB4细胞不同时间，Western blotting检测USP2底物蛋白Cyclin D1表达变化，流式细胞术检测细胞周期分布，分子对接技术分析SH与USP2结合情况。结果 体外筛选结果显示：SH抑制USP2活性，50%抑制浓度（IC50值）为69 μmol/L。Western blotting检测结果显示：SH引起USP2底物蛋白Cyclin D1表达水平降低。流式细胞术检测结果显示：SH处理NB4细胞48 h时，S和G2/M期细胞减少，并出现典型的细胞凋亡峰（Sub-G1峰）；分子对接结果显示：SH的氧原子及其骨架中心和USP2的K503、W439、R363及D440对于两者之间的结合起到重要作用。结论 SH能够抑制USP2活性，为发展新的USP2抑制剂提供了先导化合物。

Objective To identify new ubiquitin-specific protease 2 (USP2) inhibitors from natural compounds. Methods The Ub-CHOP-Reporter Kit was used to screen USP2 inhibitors. NB4 cells were treated by shionone (SH) of 100 μmol/L for different periods of time. Variations of the expression of USP2 targeted protein Cyclin D1 were detected by the Western blotting. The distribution of cell cycle was detected by the flow cytometry and molecular docking was used to analyze the binding of SH and USP2. Results The results of screening in vitro showed that SH inhibited the activity of USP2 with the 50% inhibition concentration (IC50) of 69 μmol/L. The results of Western blotting indicated that SH led to the decrease of Cyclin D1 expression. The results of flow cytometry showed that typical apoptotic peak (Sub-G1 peak) appeared and cells in S and G2/M phases decreased after being treated by SH for 48 h. The results of molecular docking indicated that the oxygen atom and skeleton core of SH and K503, W439, R363, and D440 of USP2 were essential for the binding of SH and USP2. Conclusion SH can inhibit the activity of USP2 and provide a lead compound for future development of new USP2 inhibitors.