Synthesis and structure-activity relationship of trisubstituted thiazoles as Cdc7 kinase inhibitors.

Abstract

The Cell division cycle 7 (Cdc7) protein kinase is essential for DNA replication and maintenance of genome stability. We systematically explored thiazole-based compounds as inhibitors of Cdc7 kinase activity in cancer cells. Our studies resulted in the identification of a potent, selective Cdc7 inhibitor that decreased phosphorylation of the direct substrate MCM2 in vitro and in vivo, and inhibited DNA synthesis and cell viability in vitro.

• Authors: Andreas Reichelt, Julie M Bailis, Michael D Bartberger, Guomin Yao, Hong Shu, Matthew R Kaller, John G Allen, Margaret F Weidner, Kathleen S Keegan, Jennifer H Dao
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 80 Pg. 364-82 (Jun 10 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 24793884 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Cell Cycle Proteins
• Protein Kinase Inhibitors
• Thiazoles
• CDC7 protein, human
• Protein Serine-Threonine Kinases
• MCM2 protein, human
• Minichromosome Maintenance Complex Component 2

Topics

• Animals
• Catalytic Domain
• Cell Cycle Proteins (antagonists & inhibitors, chemistry, metabolism)
• Cell Line, Tumor
• Chemistry Techniques, Synthetic
• Female
• HCT116 Cells
• Humans
• Inhibitory Concentration 50
• Male
• Mice
• Minichromosome Maintenance Complex Component 2 (metabolism)
• Molecular Docking Simulation
• Phosphorylation (drug effects)
• Protein Kinase Inhibitors (chemical synthesis, chemistry, metabolism, pharmacology)
• Protein Serine-Threonine Kinases (antagonists & inhibitors, chemistry, metabolism)
• Rats
• Structure-Activity Relationship
• Thiazoles (chemical synthesis, chemistry, metabolism, pharmacology)
• Xenograft Model Antitumor Assays