Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
Drug Discov Today. 2011 Jul;16(13-14):619-25. doi: 10.1016/j.drudis.2011.05.002. Epub 2011 May 13.
The Polo-like kinases (PLKs) have been investigated as oncology targets for several years; however, only recently have potent inhibitors been described. Here, we report on progress in the clinical validation of the PLKs as antitumor drug targets as well as recent understanding gained regarding their synergistic roles in the context of other molecular defects occurring in tumors. Also relevant to the development of PLK inhibitors as therapeutics are the putative roles of other members of this family as tumor suppressors. The resulting potential drawbacks of non-isoform selective compounds are presented. As an alternative approach to achieving PLK1 specificity, we discuss prospects for developing small molecule inhibitors of the crucial regulatory and subcellular targeting domain containing the Polo-boxes.
近年来，人们一直在研究 Polo 样激酶 (PLK) 作为肿瘤学的靶点；然而，直到最近才描述了有效的抑制剂。在这里，我们报告了 PLK 作为抗肿瘤药物靶点在临床验证方面的进展，以及最近在肿瘤中发生的其他分子缺陷的背景下对其协同作用的理解。PLK 抑制剂作为治疗药物的发展与该家族其他成员作为肿瘤抑制因子的假定作用也有关。还提出了非同工型选择性化合物的潜在缺点。作为实现 PLK1 特异性的另一种方法，我们讨论了开发包含 Polo 盒的关键调节和亚细胞靶向结构域的小分子抑制剂的前景。
