Identification of Novel Polo‐like Kinase 1 Inhibitors by a Hybrid Virtual Screening
Identification of Novel Polo‐like Kinase 1 Inhibitors by a Hybrid Virtual Screening
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DOI：
10.1111/j.1747-0285.2012.01412.x
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发表时间：
2012-08
影响因子：
3
通讯作者：
Shuai Lu;Shan-liang Sun;Haichun Liu;Yadong Chen;H. Yuan;Yi-Ping Gao;Pei Yang;T. Lu
中科院分区：
文献类型：
--
作者：
Shuai Lu;Shan-liang Sun;Haichun Liu;Yadong Chen;H. Yuan;Yi-Ping Gao;Pei Yang;T. Lu
波罗样激酶1是一个重要的和有吸引力的肿瘤靶点，在有丝分裂和胞质分裂中起关键作用。进行基于药效团和对接的组合虚拟筛选以鉴定新型波罗样激酶1抑制剂。共筛选出34个热门化合物并进行了体外试验，部分化合物显示出对波罗样激酶1和人肿瘤细胞生长的抑制作用。最有效的化合物（66）抑制波罗样激酶1，IC50值为6.99 μm。详细讨论了两种靶化合物的对接结合模型。这些化合物含有新的化学支架，可用作开发新型波罗样激酶1抑制剂的基础。
Polo‐like kinase 1 is an important and attractive oncological target that plays a key role in mitosis and cytokinesis. A combined pharmacophore‐ and docking‐based virtual screening was performed to identify novel polo‐like kinase 1 inhibitors. A total of 34 hit compounds were selected and tested in vitro, and some compounds showed inhibition of polo‐like kinase 1 and human tumor cell growth. The most potent compound (66) inhibited polo‐like kinase 1 with an IC50 value of 6.99 μm. The docked binding models of two hit compounds were discussed in detail. These compounds contained novel chemical scaffolds and may be used as foundations for the development of novel classes of polo‐like kinase 1 inhibitors.