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