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  • Title: Inhibitors of the Polo-Box Domain of Polo-Like Kinase 1.
    Author: Berg A, Berg T.
    Journal: Chembiochem; 2016 Apr 15; 17(8):650-6. PubMed ID: 26662918.
    Abstract:
    Polo-like kinase 1 (Plk1), a key player in mitosis, is overexpressed in a wide range of tumor types and has been validated as a target for tumor therapy. In addition to its N-terminal kinase domain, Plk1 harbors a C-terminal protein-protein interaction domain, referred to as the polo-box domain (PBD). Because the PBD is unique to the five-member family of polo-like kinases, and its inhibition is sufficient to inhibit the enzyme, the Plk1 PBD is an attractive target for the inhibition of Plk1 function. Although peptide-based inhibitors are invaluable tools for elucidating the nature of the binding interface, small molecules are better suited for the induction of mitotic arrest and apoptosis in tumor cells by Plk1 inhibition. This review describes the considerable progress that has been made in developing small-molecule and peptide-based inhibitors of the Plk1 PBD.
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