Chk1 inhibitors for novel cancer treatment

Anticancer Agents Med Chem. 2006 Jul;6(4):377-88. doi: 10.2174/187152006777698132.


Chemo- and radiotherapies that target DNA are the mainstay of cancer treatment. In response to DNA damage, cells are arrested in multiple checkpoints in the cell cycle to allow the damaged DNA to be repaired before progressing into mitosis. Normal cells are arrested in the G1 phase mediated by the p53 tumor suppressor, and p53-deficient cancer cells are arrested in the S or G2 phase. Checkpoint kinase 1 (Chk 1) is a serine / threonine protein kinase and a key mediator in the DNA damage-induced checkpoint network. When the G2 or S checkpoint is abrogated by the inhibition of Chk1, p53-deficient cancer cells undergo mitotic catastrophe and eventually apoptosis, whereas normal cells are still arrested in the G1 phase. Thus, Chk1 inhibitors can preferentially potentiate the efficacy of DNA damaging agents in cancer cells, and Chk1 is an attractive therapeutic target for cancer treatment, especially since approximately 50% of all human cancers are p53-deficient. This review discusses the rationale of Chk1 as an anticancer target, the structural basis for designing Chk1 inhibitors, and recently disclosed Chk1 inhibitors.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / therapeutic use
  • Cell Cycle / drug effects*
  • Checkpoint Kinase 1
  • Chemotherapy, Adjuvant / methods
  • Clinical Trials, Phase I as Topic
  • DNA Damage / drug effects*
  • Drug Synergism
  • Humans
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Kinases / drug effects
  • Protein Kinases / metabolism*


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1