A thienopyrimidine derivative induces growth inhibition and apoptosis in human cancer cell lines via inhibiting Aurora B kinase activity.

Abstract

Aurora kinases play a key role in the regulation of mitosis and have been regarded as promising targets of cancer therapy. In this paper we describe a thienopyrimidine derivative (S7), a novel potent ATP-competitive hit inhibitor of Aurora B kinase screened through a HTS system, with the IC50 141.12 nM in the biochemical kinase activity assay. Human tumor cells treated with S7 showed dose-dependent inhibition of auto-phosphorylation of Aurora B on Thr232 and another widely-used marker specific for Aurora B kinase, the phosphorylation of Histone H3 (Ser 10), demonstrating endogenous Aurora B kinase activity were inhibited at cellular level. Moreover, S7 treatment induced proliferation inhibition, colony formation inhibition and apoptosis of human tumor cell lines in a dose- and time-dependent manner.

• Authors: Jie Li, Hairong Hu, Qingyu Lang, Haoxing Zhang, Qiang Huang, Yuanyuan Wu, Long Yu
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 65 Pg. 151-7 (Jul 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23707920 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Pyrimidines
• thienopyrimidine
• Aurora Kinase B

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Aurora Kinase B (antagonists & inhibitors, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HCT116 Cells
• HeLa Cells
• Hep G2 Cells
• Humans
• MCF-7 Cells
• Models, Molecular
• Molecular Structure
• Protein Kinase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Pyrimidines (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship