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KMID : 0578320110320030209
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Molecules and Cells
2011 Volume.32 No. 3 p.209 ~ p.220
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Plk1-Targeted Small Molecule Inhibitors: Molecular Basis for Their Potency and Specificity
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Ravichandran N. Murugan
Park Jung-Eun
Kim Eun-Hee
Shin Song-Yub
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Abstract
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Members of polo-like kinases (collectively, Plks) have been identified in various eukaryotic organisms and play pivotal roles in cell proliferation. They are characterized by the presence of a distinct region of homology in the C-terminal noncatalytic domain, called polo-box domain (PBD). Among them, Plk1 and its functional homologs in other organisms have been best characterized because of its strong association with tumorigenesis. Plk1 is overexpressed in a wide spectrum of cancers in humans, and is thought to be an attractive anti-cancer drug target. Plk1 offers, within one molecule, two functionally different drug targets with distinct properties-the N-terminal catalytic domain and the C-terminal PBD essential for targeting the catalytic activity of Plk1 to specific subcellular locations. In this review, we focused on discussing the recent development of small-molecule and phosphopeptide inhibitors for their potency and specificity against Plk1. Our effort in understanding the binding mode of various inhibitors to Plk1 PBD are also presented.
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KEYWORD
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cancer therapy, inhibitors, Plk1, polo-box domain (PBD), polo-like kinase
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