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 .