Inhibitors of checkpoint kinases: from discovery to the clinic

Curr Opin Drug Discov Devel. 2007 Jul;10(4):473-86.


Checkpoint kinase 1 (CHK1) is a member of the serine/ threonine kinase family. CHK1 functions as a regulatory kinase in cell-cycle progression and is the main effector of theDNA-damage response within the cell. Over the past few years, a large number of novel inhibitors of CHK1 have been discovered that encompass an enormous area of chemical space and diversity and, in more recent reports, many of these inhibitors have been demonstrated preclinically to sensitize tumors to a wide variety of DNA-damaging agents. This review focuses on advances reported both in the literature and at conferences from 2005 to date concerning the chemical design and optimization of checkpoint kinase inhibitors for the treatment of cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Checkpoint Kinase 1
  • DNA Damage / drug effects
  • Drug Design*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / classification
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Neoplasms / drug therapy*
  • Protein Kinases / drug effects*
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1