Skip to main content

In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1.

Publication ,  Journal Article
Lansing, TJ; McConnell, RT; Duckett, DR; Spehar, GM; Knick, VB; Hassler, DF; Noro, N; Furuta, M; Emmitte, KA; Gilmer, TM; Mook, RA; Cheung, M
Published in: Mol Cancer Ther
February 2007

Polo-like kinase 1 (PLK1) plays key roles in the regulation of mitotic progression, including mitotic entry, spindle formation, chromosome segregation, and cytokinesis. PLK1 expression and activity are strongly linked to proliferating cells. Many studies have shown that PLK1 expression is elevated in a variety of tumors, and high expression often correlates with poor prognosis. Using a variety of methods, including small-molecule inhibition of PLK1 function and/or activity, apoptosis in cancer cell lines, cell cycle arrest in normal cell lines, and antitumor activity in vivo have been observed. In the present study, we have examined the in vitro biological activity of a novel and selective thiophene benzimidazole ATP-competitive inhibitor of PLK1 and PLK3 (5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-{[2-(trifluoromethyl)-benzyl]oxy}thiophene-2-carboxamide, called compound 1). Compound 1 has low nanomolar activity against the PLK1 and PLK3 enzymes and potently inhibits the proliferation of a wide variety of tumor cell lines. In the lung adenocarcinoma cell line NCI-H460, compound 1 induces a transient G(2)-M arrest, mitotic spindle defects, and a multinucleate phenotype resulting in apoptosis, whereas normal human diploid fibroblasts arrest in G(2)-M and show little apoptosis. We also describe a cellular mechanistic assay that was developed to identify potent intracellular inhibitors of PLK1. In addition to its potential as a therapeutic agent for treating cancer, compound 1 is also a useful tool molecule for further investigation of the biological functions of PLK1 and PLK3.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Cancer Ther

DOI

ISSN

1535-7163

Publication Date

February 2007

Volume

6

Issue

2

Start / End Page

450 / 459

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Thiophenes
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Polo-Like Kinase 1
  • Oncology & Carcinogenesis
  • Molecular Structure
  • Microscopy, Fluorescence
  • Lung Neoplasms
  • Immunoblotting
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lansing, T. J., McConnell, R. T., Duckett, D. R., Spehar, G. M., Knick, V. B., Hassler, D. F., … Cheung, M. (2007). In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol Cancer Ther, 6(2), 450–459. https://doi.org/10.1158/1535-7163.MCT-06-0543
Lansing, Timothy J., Randy T. McConnell, Derek R. Duckett, Glenn M. Spehar, Victoria B. Knick, Daniel F. Hassler, Nobuhiro Noro, et al. “In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1.Mol Cancer Ther 6, no. 2 (February 2007): 450–59. https://doi.org/10.1158/1535-7163.MCT-06-0543.
Lansing TJ, McConnell RT, Duckett DR, Spehar GM, Knick VB, Hassler DF, et al. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol Cancer Ther. 2007 Feb;6(2):450–9.
Lansing, Timothy J., et al. “In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1.Mol Cancer Ther, vol. 6, no. 2, Feb. 2007, pp. 450–59. Pubmed, doi:10.1158/1535-7163.MCT-06-0543.
Lansing TJ, McConnell RT, Duckett DR, Spehar GM, Knick VB, Hassler DF, Noro N, Furuta M, Emmitte KA, Gilmer TM, Mook RA, Cheung M. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol Cancer Ther. 2007 Feb;6(2):450–459.

Published In

Mol Cancer Ther

DOI

ISSN

1535-7163

Publication Date

February 2007

Volume

6

Issue

2

Start / End Page

450 / 459

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Thiophenes
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Polo-Like Kinase 1
  • Oncology & Carcinogenesis
  • Molecular Structure
  • Microscopy, Fluorescence
  • Lung Neoplasms
  • Immunoblotting