Tong Xin-Yu, Liao Xuan, Gao Min, Lv Bo-Min, Chen Xiao-Hui, Chu Xin-Yi, Zhang Qing-Ye, Zhang Hong-Yu
Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, China.
Front Mol Biosci. 2020 Mar 31;7:44. doi: 10.3389/fmolb.2020.00044. eCollection 2020.
Recent studies have revealed the important role of NUDT5 in estrogen signaling and breast cancer, but research on the corresponding targeted therapy has just started. Drug repositioning strategy can effectively reduce the time and economic resources spent on drug discovery. To find novel inhibitors of NUDT5, we investigated the previously identified connectivity map-based drug association models and found eighteen FDA approved drugs as candidates. The molecular docking and molecular dynamic simulation were performed and revealed that fourteen organic drugs have the potential to bind the NUDT5 target. Eight representative drugs were selected to perform the cell line viability inhibition analysis, and the results showed that seven of them were able to suppress MCF7 breast cancer cells. Two drugs, nomifensine and isoconazole, showed lower IC than the known antiestrogens raloxifene and tamoxifen, and they deserve further pharmacodynamic investigations to test their feasibility for use as NUDT5 inhibitors.
最近的研究揭示了NUDT5在雌激素信号传导和乳腺癌中的重要作用，但针对相应靶向治疗的研究才刚刚开始。药物重定位策略可以有效减少药物研发所花费的时间和经济资源。为了寻找NUDT5的新型抑制剂，我们研究了先前确定的基于连接图谱的药物关联模型，并发现18种美国食品药品监督管理局（FDA）批准的药物可作为候选药物。进行了分子对接和分子动力学模拟，结果表明14种有机药物具有与NUDT5靶点结合的潜力。选择了8种代表性药物进行细胞系活力抑制分析，结果显示其中7种能够抑制MCF7乳腺癌细胞。诺米芬辛和异康唑这两种药物的半数抑制浓度（IC）低于已知的抗雌激素药物雷洛昔芬和他莫昔芬，它们值得进一步进行药效学研究，以测试其作为NUDT5抑制剂使用的可行性。
