目的 通过虚拟筛选的方法发现SUMO特异性蛋白酶1（SENP1）新的小分子抑制剂，并对其生物学活性进行体外验证。方法 通过对小分子数据库虚拟筛选，得到可能的SENP1小分子抑制剂。化学合成筛选得到的JK043，经SENP1的体外测试体系验证该小分子的抑制活性，计算IC50。构建对接模型，观察JK043与SENP1的作用模式。结果 通过体外活性测试发现，化学合成的JK043能够抑制SENP1的活性，IC50值为1.339 μmol/L。通过对接模型发现，JK043与SENP1蛋白的465W、468D、529H、597Q存在相互作用关系。结论 发现并合成JK043，其对SENP1有一定的体外抑制活性。

Objective To identify novel small molecule inhibitors of SENP1 by virtual screening and evaluate the biological activity in vitro. Methods The possible small molecule inhibitors of SENP1 were selected from the small molecule database by virtual screening. Screened JK043 were chemically synthesized and the inhibitory effect of JK043 on the activity of SENP1 was evaluated by the in vitro test system of SENP1. IC50 was calculated. The action mode between JK043 and SENP1 was then observed through the docking model. Results The activity test in vitro showed that chemically synthesized JK043 could inhibit the activity of SENP1 and the valued of IC50 was 1.339 μmol/L. The docking model indicated that JK043 interacted with 465W, 468D, 529H, and 597Q of SENP1 protein. Conclusion JK043 has been identified and synthesized, which can inhibit the activity of SENP1 in vitro to a certain extent.