机构：[1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.四川大学华西医院[2]State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.四川大学华西医院[3]Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis 38163, Tennessee, United States.
Polo-like kinase 1 (PLK1) plays an important role in a variety of cellular functions, including the regulation of mitosis, DNA replication, autophagy, and the epithelial-mesenchymal transition (EMT). PLK1 overexpression is often associated with cell proliferation and poor prognosis in cancer patients, making it a promising antitumor target. To date, at least 10 PLK1 inhibitors (PLK1i) have been entered into clinical trials, among which the typical kinase domain (KD) inhibitor BI 6727 (volasertib) was granted "breakthrough therapy designation" by the FDA in 2013. Unfortunately, many other KD inhibitors showed poor specificity, resulting in dose-limiting toxicity, which has greatly impeded their development. Researchers recently discovered many PLK1i with higher selectivity, stronger potency, and better absorption, distribution, metabolism, and elimination (ADME) characteristics. In this review, we emphasize the structure-activity relationships (SARs) of PLK1i, providing insights into new drugs targeting PLK1 for antitumor clinical practice.
基金：
Sichuan Science and Technology
Program (2019YFS0003), National Natural Science Foundation
of China (82073318, 81922064, 81903502), National
Major Scientific and Technological Special Project for
Significant New Drugs Development (2018ZX09201018-021),
The 1.3.5 Project for Disciplines of Excellence, West China
Hospital, Sichuan University (ZYGD20001) and Natural
Science Foundation of Sichuan Province (2022NSFSC1365).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|1 区医学
小类|1 区药物化学
最新[2023]版：
大类|1 区医学
小类|1 区药物化学
第一作者：
第一作者机构：[1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.[2]State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
共同第一作者：
通讯作者：
通讯机构：[1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.[2]State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
推荐引用方式(GB/T 7714)：
Zhang Jifa,Zhang Lele,Wang Jiaxing,et al.Polo-like Kinase 1 Inhibitors in Human Cancer Therapy: Development and Therapeutic Potential[J].Journal of medicinal chemistry.2022,doi:10.1021/acs.jmedchem.2c00614.
APA：
Zhang Jifa,Zhang Lele,Wang Jiaxing,Ouyang Liang&Wang Yuxi.(2022).Polo-like Kinase 1 Inhibitors in Human Cancer Therapy: Development and Therapeutic Potential.Journal of medicinal chemistry,,
MLA：
Zhang Jifa,et al."Polo-like Kinase 1 Inhibitors in Human Cancer Therapy: Development and Therapeutic Potential".Journal of medicinal chemistry .(2022)
医学