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Chk1 inhibitors for novel cancer treatment.
- Source :
-
Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2006 Jul; Vol. 6 (4), pp. 377-88. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents therapeutic use
Checkpoint Kinase 1
Chemotherapy, Adjuvant methods
Clinical Trials, Phase I as Topic
Drug Synergism
Humans
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors therapeutic use
Protein Kinases drug effects
Antineoplastic Agents chemistry
Cell Cycle drug effects
DNA Damage drug effects
Protein Kinase Inhibitors chemistry
Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1871-5206
- Volume :
- 6
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Anti-cancer agents in medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16842237
- Full Text :
- https://doi.org/10.2174/187152006777698132