Developments of Polo-like Kinase 1 (Plk1) Inhibitors as Anti-Cancer Agents

Title:Developments of Polo-like Kinase 1 (Plk1) Inhibitors as Anti-Cancer Agents

Volume: 13 Issue: 14

Author(s): Shanshan Li, Yingjie Zhang and Wenfang Xu

Affiliation:

Keywords: Antitumor activity, clinical, inhibitors, Polo-like kinases, pre-clinical, selectivity, SAR.

Abstract: 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.

Cite this article as:

Li Shanshan, Zhang Yingjie and Xu Wenfang, Developments of Polo-like Kinase 1 (Plk1) Inhibitors as Anti-Cancer Agents, Mini-Reviews in Medicinal Chemistry 2013; 13 (14) . https://dx.doi.org/10.2174/13895575113136660103