Properties and Potential Applications of Chemical Inhibitors of Cyclin-Dependent Kinases

Cyclin-dependent kinases (CDKs) trigger and co-ordinate the cell division cycle phases. They also play a role in neuronal cells and in the control of transcription. Intensive screening has led in the past few years to the identification of a series of chemical inhibitors of CDKs. Some of these compo...

Full description

Saved in:
Bibliographic Details
Published in:Pharmacology & therapeutics (Oxford) 1999-05, Vol.82 (2), p.279-284
Main Authors: Meijer, Laurent, Leclerc, Sophie, Leost, Maryse
Format: Article
Language:English
Subjects:
AIDS/HIV
cell cycle
Cell Division - drug effects
cell proliferation
Clinical Trials as Topic
cyclin-dependent kinases
Cyclin-Dependent Kinases - antagonists & inhibitors
Enzyme Inhibitors - pharmacology
Enzyme Inhibitors - therapeutic use
Humans
inhibitors
Protein kinase
Sensitivity and Specificity
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cyclin-dependent kinases (CDKs) trigger and co-ordinate the cell division cycle phases. They also play a role in neuronal cells and in the control of transcription. Intensive screening has led in the past few years to the identification of a series of chemical inhibitors of CDKs. Some of these compounds display remarkable selectivity and efficiency (IC 50 < 25 nM). Many have been co-crystallised with CDK2, and their atomic interactions with the kinase have been analysed in detail: all are located in the ATP-binding pocket of the enzyme. These inhibitors are antimitotic, they arrest cells in G1 and, at higher doses, in G2/M. Furthermore, they facilitate or even trigger apoptosis in proliferating cells. In contrast, they protect neuronal cells from apoptosis. The potential use of these inhibitors is being extensively evaluated in cancer chemotherapy (clinical trials, Phase I and II). Possible clinical applications are being investigated in other fields: cardiovascular (restenosis, tumoural angiogenesis, atherosclerosis), nephrology (glomerulonephritis), dermatology (psoriasis), parasitology (unicellular parasites such as Plasmodium, Trypanosoma, Toxoplasma, etc.), neurology (Alzheimer’s disease), viral infections (cytomegalovirus, human immunodeficiency virus, herpes). We anticipate the discovery of novel selective and powerful inhibitors in the near future, and hope for their efficient applications in various human diseases.
ISSN:0163-7258
1879-016X
DOI:10.1016/S0163-7258(98)00057-6