Department of Medicinal Chemistry, School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR China.
Yangtze River Pharmaceutical Group Shanghai Haini Pharmaceutical Co., Ltd. Pudong, Shanghai, 201100, PR China.
Eur J Med Chem. 2021 May 5;217:113314. doi: 10.1016/j.ejmech.2021.113314. Epub 2021 Mar 16.
Polo-like kinases (PLKs) play important roles in regulating multiple aspects of cell cycle and cell proliferation. In many cancer types, PLK family members are often dysregulated, which can lead to uncontrolled cell proliferation and aberrant cell division and has been shown to associate with poor prognosis of cancers. The key roles of PLK kinases in cancers lead to an enhanced interest in them as promising targets for anticancer drug development. In consideration of PLK inhibitors and some other anticancer agents, such as BRD4, EEF2K and Aurora inhibitors, exert synergy effects in cancer cells, dual-targeting of PLK and other cancer-related targets is regarded as an rational and potent strategy to enhance the effectiveness of single-targeting therapy for cancer treatment. This review introduces the PLK family members at first and then focuses on the recent advances of single-target PLK inhibitors and summarizes the corresponding SARs of them. Moreover, we discuss the synergisms between PLK and other anti-tumor targets, and sum up the current dual-target agents based on them.
丝氨酸/苏氨酸激酶（PLKs）在调节细胞周期和细胞增殖的多个方面发挥重要作用。在许多癌症类型中，PLK 家族成员通常失调，这可能导致不受控制的细胞增殖和异常细胞分裂，并与癌症的预后不良相关。PLK 激酶在癌症中的关键作用使得它们成为有希望的抗癌药物开发靶点的兴趣增强。考虑到 PLK 抑制剂和其他一些抗癌药物，如 BRD4、EEF2K 和 Aurora 抑制剂，在癌细胞中具有协同作用，PLK 和其他与癌症相关的靶点的双重靶向被认为是增强单一靶向治疗癌症的有效性的合理而有效的策略。本综述首先介绍了 PLK 家族成员，然后重点介绍了单一靶向 PLK 抑制剂的最新进展，并总结了它们的相应 SAR。此外，我们讨论了 PLK 与其他抗肿瘤靶点之间的协同作用，并根据这些靶点总结了目前的双重靶向药物。
