Polo 样激酶 (PLK) 有五种亚型，所有亚型在细胞周期和细胞增殖中都发挥着至关重要的作用，为药物设计和癌症及其他相关疾病的治疗提供了机会。值得注意的是，PLK1 和 PLK4 作为癌症药物靶点已被广泛研究。 PLK 的一个显着特征是存在独特的 polo-box 结构域 (PBD)，该结构域调节激酶活性和亚细胞定位。这为专门针对 PLK 提供了可能性。本文概述了 PLK 在各种癌症和相关疾病中的作用，以及涉及 PLK 的药物开发，特别关注 PLK1 和 PLK4。总结了2018年至今在专利或文献中公开的PLK1和PLK4抑制剂，这些抑制剂来源于SciFinder和WIPO数据库。经过二十年的PLK药物开发，多种药物进入了治疗以下疾病的临床试验：然而，许多癌症尚未获得批准。进一步阐明PLKs的作用机制，识别和开发高选择性的ATP竞争性抑制剂、高效的类药PBD抑制剂、降解剂等，可能为癌症治疗和多种非肿瘤疾病的治疗提供新的机遇。基于 PLK 抑制的联合疗法可能是另一种有用的策略。

Polo-like kinases (PLKs) have five isoforms, all of which play crucial roles in cell cycle and cell proliferation, offering opportunities for drug design and treatment of cancers and other related diseases. Notably, PLK1 and PLK4 have been extensively investigated as cancer drug targets. One distinctive feature of PLKs is the presence of a unique polo-box domain (PBD), which regulates kinase activity and subcellular localization. This provides possibilities for specifically targeting PLKs.This article provides an overview of the roles of PLKs in various cancers and related diseases, as well as the drug development involving PLKs, with a particular focus on PLK1 and PLK4. It summarizes the PLK1 and PLK4 inhibitors that have been disclosed in patents or literature (from 2018 - present), which were sourced from SciFinder and WIPO database.After two decades of drug development on PLKs, several drugs progressed into clinical trials for the treatment of many cancers, however, none of them has been approved yet. Further elucidating the mechanisms of PLKs and identifying and developing highly selective ATP-competitive inhibitors, highly potent drug-like PBD inhibitors, degraders, etc. may provide new opportunities for cancer therapy and the treatment for several nononcologic diseases. PLKs inhibition-based combination therapies can be another helpful strategy.