Polo-like kinase 1 (Plk1) plays key roles in regulating various mitotic processes that are critical for cellular proliferation. A growing body of evidence suggests that Plk1 overexpression is tightly associated with the development of human cancers. Interestingly, various types of cancer cells are shown to be addicted to a high level of Plk1, and the reversal of Plk1 addiction appears to be an effective strategy for selectively killing cancer cells, but not normal cells. Therefore, Plk1 is considered an attractive anticancer drug target. Over the years, a large number of inhibitors that target the catalytic activity of Plk1 have been developed. However, these inhibitors exhibit significant levels of cross-reactivity with related kinases, including Plk2 and Plk3. Consequently, as an alternative approach for developing anti-Plk1 therapeutics, substantial effort is under way to develop inhibitors that target the C-terminal protein–protein interaction domain of Plk1, called the polo-box domain (PBD). In this communication, I will discuss the pros and cons of targeting the PBD in comparison to those of targeting the ATP-binding site within the kinase domain.

中文翻译：

---

对 polo 样激酶 1 的 polo-box 域进行一些研究

Polo 样激酶 1 (Plk1) 在调节对细胞增殖至关重要的各种有丝分裂过程中起关键作用。越来越多的证据表明 Plk1 过表达与人类癌症的发展密切相关。有趣的是，各种类型的癌细胞都表现出对高水平的 Plk1 上瘾，而 Plk1 成瘾的逆转似乎是选择性杀死癌细胞而非正常细胞的有效策略。因此，Plk1 被认为是一个有吸引力的抗癌药物靶点。多年来，已经开发了大量针对 Plk1 催化活性的抑制剂。然而，这些抑制剂与相关激酶（包括 Plk2 和 Plk3）表现出显着水平的交叉反应。因此，作为开发抗 Plk1 疗法的替代方法，正在努力开发靶向 Plk1 的 C 端蛋白质-蛋白质相互作用域的抑制剂，称为 polo-box 域 (PBD)。在本次交流中，我将讨论与靶向激酶结构域内的 ATP 结合位点相比，靶向 PBD 的利弊。