Polo-Like Kinase 1（PLK1）是有丝分裂的关键调节因子，其过度表达经常在人类多种癌症中观察到，通常与低存活率有关。因此，它被认为是癌症治疗发展的潜在和有吸引力的靶点。Polo-like激酶家族以存在于唯一的C末端polobox结构域（PBD）为特征，该结构域参与调节激酶活性和亚细胞定位。在PLK1提供的两个具有不同特性的功能必需，可药物处理的位点中，针对PBD是癌症治疗发展的替代途径。 从首次发现的肽PBD抑制剂到类肽和最近的药物样小分子，已经取得了显著进展。本文讨论了针对PBD而不是ATP结合位点的理论基础以及最近的进展、挑战和前景。PBD已成为抑制PLK1的可行替代目标，并且在使用化合物阐明活性调节的机制方面以及确定PBD的作用方面取得了进展。研究结果证明了体内有效性的概念，表明PBD结合剂在临床开发中很有前途。

Polo Like Kinase 1 (PLK1) is a key regulator of mitosis and its overexpression is frequently observed in a wide variety of human cancers, while often being associated with poor survival rates. Therefore, it is considered a potential and attractive target for cancer therapeutic development. The Polo like kinase family is characterized by the presence of a unique C terminal polobox domain (PBD) involved in regulating kinase activity and subcellular localization. Among the two functionally essential, druggable sites with distinct properties that PLK1 offers, targeting the PBD presents an alternative approach for therapeutic development.Significant progress has been made in progressing from the peptidic PBD inhibitors first identified, to peptidomimetic and recently drug-like small molecules. In this review, the rationale for targeting the PBD over the ATP binding site is discussed, along with recent progress, challenges, and outlook.The PBD has emerged as a viable alternative target for the inhibition of PLK1, and progress has been made in using compounds to elucidate mechanistic aspects of activity regulation and in determining roles of the PBD. Studies have resulted in proof of concept of in vivo efficacy suggesting promise for PBD binders in clinical development.