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PLK1 as a potential drug target in cancer therapy
Author(s) -
Goh Kee Chuan,
Wang Haishan,
Yu Niefang,
Zhou Yifa,
Zheng Yin,
Lim ZeYi,
Sangthongpitag Kanda,
Fang Lijuan,
Du Mark,
Wang Xukun,
Jefferson A. B.,
Rose Janet,
Shamoon Blanche,
Reinhard Christoph,
Carte Brad,
Entzeroth Michael,
Ni BinHui,
Taylor Marcia L.,
Stünkel Walter
Publication year - 2004
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10392
Subject(s) - plk1 , cell cycle , cancer research , kinase , polo like kinase , cell cycle checkpoint , cell culture , biology , cell growth , cancer cell , drug discovery , cell , drug , chemistry , microbiology and biotechnology , cancer , pharmacology , biochemistry , genetics
Polo‐like kinase 1 (PLK1) has been shown to be involved in cell cycle progression of rapidly proliferating, nontransformed cells as well as tumor cells. In cancer, overexpression of PLK1 contributes to the malignant state by aberrant cell cycle regulation at the G2/M phase. We attempted to validate PLK1 function in cell‐based assays using antisense oligonucleotide knockout approaches. Our own results and published findings of other groups have led to the conclusion that PLK1 is a logical point for pharmacological intervention. HTS campaigns performed against the recombinant PLK1‐protein led to the identification of two PLK1 inhibitory scaffolds, one containing a 7‐azapteridine ring system, the other a fused tetracyclic ketone system. These compounds showed low micromolar antiproliferative activity towards SW620, a human colon cancer cell line, most likely through cell cycle arrest at the G2/M phase. Our data suggest that PLK1 may serve as a target for discovering small molecule anticancer agents. Drug Dev. Res. 62:349–361, 2004. © 2004 Wiley‐Liss, Inc.