S期激酶相关蛋白2和赖氨酸特异性去甲基酶1双靶抑制剂的虚拟筛选  

Computer-assisted virtual screening of dual-target inhibitors of skp2 and LSD1

作　　者：张明雪 冯蓉 何俊[3] 许建 龚军 师健友 ZHANG Mingxue;FENG Rong;HE Jun;XU Jian;GONG Jun;SHI Jianyou(State Key Laboratory of Southwestern Chinese Medicine Resources,Department of Pharmacy,Chengdu University of TCM,Chengdu,Sichuan,611137 P.R.China;Pharmacy Department of Yunnan Maternal and Child Health Hospital,Kunming,Yunnan,650051 P.R.China;West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China;Sichuan Provincial Peoples Hospital,Sichuan Academy of Medical Sciences,Chengdu,Sichuan,610031 P.R.China)

机构地区：[1]成都中医药大学药学院、西南特色中药资源国家重点实验室,四川成都611137 [2]云南省妇幼保健院药剂科,云南昆明650051 [3]四川大学华西药学院,四川成都610041 [4]四川省医学科学院四川省人民医院,四川成都610031

出　　处：《华西药学杂志》2024年第5期522-526,共5页West China Journal of Pharmaceutical Sciences

基　　金：西南特色中药资源国家重点实验室开放基金(2021HX026);四川省科技计划项目(2022YFS0224)。

摘　　要：目的筛选S期激酶相关蛋白2(skp2)和赖氨酸特异性去甲基酶1(LSD1)双靶点抑制剂。方法采用计算机辅助药物设计,经过分子对接、虚拟筛选以及定量构效关系(QSAR)模型预测,从小分子数据库中筛选对两个靶点活性较好的化合物。结果与结论得到了6个对接打分较好的化合物。QSAR模型显示其对skp2和LSD1均有较理想的抑制效果,为后续skp2/LSD1双靶点抑制剂的开发提供了思路。OBJECTIVE To screen S-phase kinase-related protein 2(skp2)and lysine specific demethylase 1(LSD1)dual target inhibitors.METHODS Based on computer-aided drug design,the compounds with good activity against two targets were screened from the small molecule database by molecular docking,virtual screening,and quantitative structure-activity relationship(QSAR)model prediction.RESULTS and CONCLUSION Six compounds were identified that exhibited favorable docking score results compound.The QSAR model demonstrated that the compounds displayed inhibitory effects on skp2 and LSD1,suggesting potential avenues for the subsequent development of skp2/LSD1 dual-target inhibitors.

关 键 词：S期激酶相关蛋白2 赖氨酸特异性去甲基酶1 小分子抑制剂 分子对接 计算机辅助药物设计 虚拟筛选 双靶点抑制剂 定量构效关系 

分 类 号：R914[医药卫生—药物化学]