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Open AccessArticle

Discovery of a Potent PLK1-PBD Small-Molecule Inhibitor as an Anticancer Drug Candidate through Structure-Based Design

1
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China
2
State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(23), 4351; https://doi.org/10.3390/molecules24234351
Received: 26 October 2019 / Revised: 26 November 2019 / Accepted: 26 November 2019 / Published: 28 November 2019
(This article belongs to the Section Computational and Theoretical Chemistry)
Polo-box domain of polo-like kinase 1 (PLK1-PBD) has a pivotal role in cell proliferation and could be implicated as a potential anticancer target. Although some small-molecule inhibitors have been developed, their clinical application has been restricted by the poor selectivity. Therefore, there is an urgent need to develop effective PLK1-PBD inhibitors. Herein, we have developed a virtual screening protocol to find PLK1-PBD inhibitors by using combination of structure-based pharmacophore modeling and molecular docking. This protocol was successfully applied to screen PLK1-PBD inhibitors from specs database. MTT assay indicated that five screened hits suppressed the growth of HeLa cells. Particularly, hit-5, as a selective PLK1 inhibitor targeting PLK1-PBD, significantly inhibited the progression of HeLa cells-derived xenograft, with no obvious side effects. This work demonstrates that hit-5 may be a potential anticancer agent. View Full-Text
Keywords: polo-box domain; pharmacophore modeling; molecular docking; cancer therapy polo-box domain; pharmacophore modeling; molecular docking; cancer therapy
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MDPI and ACS Style

Zhou, Y.; Yan, F.; Huo, X.; Niu, M.-M. Discovery of a Potent PLK1-PBD Small-Molecule Inhibitor as an Anticancer Drug Candidate through Structure-Based Design. Molecules 2019, 24, 4351.

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