Background: The checkpoint kinases, Chk1 and Chk2 are Ser/Thr protein kinases, which function as key regulatory kinases in cellular DNA damage response pathways limiting cell-cycle progression in the presence of DNA damage. The development of checkpoint kinase inhibitors for the treatment of cancer has been a major objective in drug discovery over the past decade, as evidenced by three checkpoint kinase inhibitors entering clinic trials since late 2005. Objectives: This review describes and discusses the most recent inhibitors of checkpoint kinases Chk1 and Chk2, as reported in the patent literature, including an evaluation of chemical structure and biological activity. Methods: Using a variety of approaches, we searched and analyzed all patent applications claiming chemical matter in which Chk1 or Chk2 were stated as targets of inhibition from January 2006 through August 2008. Conclusions: A large number of chemically diverse Chk1 and Chk2 kinase inhibitors have appeared in the recent patent literature. Common structural motifs of the checkpoint kinase inhibitors were identified. There are currently three checkpoint kinase inhibitors in clinical development, a continuing effort by the pharmaceutical industry to identify novel scaffolds for checkpoint kinase inhibition.
- DNA damage