Format

Send to

Choose Destination
Eur J Med Chem. 2014 Jun 10;80:364-82. doi: 10.1016/j.ejmech.2014.04.013. Epub 2014 Apr 5.

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

Author information

1
Medicinal Chemistry, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: Andreas.Reichelt@amgen.com.
2
Oncology Research, Amgen, Inc., 1201 Amgen Court West, Seattle, WA 98119, USA.
3
Molecular Structure and Characterization, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
4
Medicinal Chemistry, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.

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.

KEYWORDS:

Cdc7; DNA replication; Kinase inhibitor; MCM2; Thiazole

PMID:
24793884
DOI:
10.1016/j.ejmech.2014.04.013
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center