作用于Polo-box结构域的Polo样激酶1抑制剂的研究进展

Research progress of Polo-like kinase 1 inhibitors targeting Polo-box domain

Polo样激酶1(Plk1)的过度表达在多种肿瘤的发生及发展过程中起着关键作用,目前已有多个不同结构的作用于ATP结合口袋和底物结合位点的小分子Plk1抑制剂进入临床研究。Polo-box结构域(PBD)是Plks特有的结构域,对Plk1在细胞中的定位及其与底物的结合有重要作用,被认为是另一个靶向型Plk1抑制剂研究的潜在靶点。本文介绍了Plk1的PBD功能,从小分子化合物和含有磷酸化的丝氨酸/苏氨酸短肽及其衍生物两个方面综述了作用于PBD的Plk1抑制剂的最新研究进展,并对这类抑制剂的研究前景进行了展望。

The over-expression of Polo-like kinase 1 （Plkl） is critical in the production and progression of multi- ple human tumors and is recognized as an effective target for the development of novel anti-cancer drugs. Currently a variety of small molecules targeting ATP or substrate binding sites have entered different stages of clinical trials. Polo-box domain（PBD） is a unique domain of Plks which plays an important role in the sub- cellular location of Plks and in the recognition of their substrates, therefore it has become an attractive target for the development of novel target-directed Plkl inhibitors. In this paper, PBD function of Plkl was introduced, the progress of small molecule and phosphoserine/phosphothreonine contained short peptide Plkl inhibitors targeting PBD is summarized. Further development of this kind of inhibitors is also proposed.