标题：Developments of polo-like kinase 1 (Plk1) inhibitors as anti-cancer agents
作者机构：[Li, S] Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong, 250012, China;[ Zhang, Y] Department of Medicina 更多
通讯作者地址：[Xu, WF]Shandong Univ, Sch Pharm, Dept Med Chem, Jinan 250012, Shandong, Peoples R China.
来源：Mini reviews in medicinal chemistry
关键词：Antitumor activity;Clinical;Inhibitors;Polo-like kinases;Pre-clinical;SAR;Selectivity
摘要：Polo-like kinases (Plks) are a family of serine/threonine kinases with a highly conserved N-terminal Ser/Thr kinase catalytic domain and a C-terminal region that play crucial roles in cell cycle progression. Plk1, playing a key role in multiple steps of mitotic progression, is the most studied member of the family. It is overexpressed in a wide spectrum of cancer types and is a promising target in oncology. Most of Plk1 inhibitors competitively bind to the ATP-binding site, which is characterized with unique features. Other inhibitors target regions outside the ATP pocket. In this review some pre-clinical or clinical Plk1 inhibitors are reported, focusing on SAR studies and biological activities, including the kinase activity, in vitro and in vivo anti-tumor efficacy. Those studies exhibited the inhibitors\' significant therapeutic effects. Moreover, combination therapies of these Plk1 inhibitors with other anticancer drugs resulted with synergistic effects.