Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance

Seliciclib (R-Roscovitine) was identified as an inhibitor of CDKs and has undergone drug development and clinical testing as an anticancer agent. In this review, the authors describe the discovery of Seliciclib and give a brief summary of the biology of the CDKs Seliciclib inhibits. An overview of t...

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Bibliographic Details
Published in:Journal of biotechnology 2015-05, Vol.202, p.40-49
Main Authors: Khalil, Hilal S., Mitev, Vanio, Vlaykova, Tatyana, Cavicchi, Laura, Zhelev, Nikolai
Format: Article
Language:English
Subjects:
Animals
Anticancer properties
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Biology
CDK
Cell Proliferation - drug effects
Clinical Trials as Topic
Cyclin-Dependent Kinases - antagonists & inhibitors
Drug Repositioning - methods
Drugs
Humans
In vitro testing
Inhibitors
Kinases
Mathematical models
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Purines - pharmacology
Purines - therapeutic use
Seliciclib
Summaries
Systems biology
Systems Biology - methods
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Summary:Seliciclib (R-Roscovitine) was identified as an inhibitor of CDKs and has undergone drug development and clinical testing as an anticancer agent. In this review, the authors describe the discovery of Seliciclib and give a brief summary of the biology of the CDKs Seliciclib inhibits. An overview of the published in vitro and in vivo work supporting the development as an anti-cancer agent, from in vitro experiments to animal model studies ending with a summary of the clinical trial results and trials underway is presented. In addition some potential non-oncology applications are explored and the potential mode of action of Seliciclib in these areas is described. Finally the authors argue that optimisation of the therapeutic effects of kinase inhibitors such as Seliciclib could be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division.
ISSN:0168-1656
1873-4863
DOI:10.1016/j.jbiotec.2015.02.032