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Structure-based discovery of cyclin-dependent protein kinase inhibitors

Lookup NU author(s): Dr Mathew Martin, Professor Jane Endicott, Professor Martin NobleORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Portland Press Ltd., 2017.

For re-use rights please refer to the publisher's terms and conditions.


The cell fate-determining roles played by members of the cyclin-dependent protein kinase (CDK) family explain why their dysregulation can promote proliferative diseases, and identify them as potential targets for drug discovery in oncology and beyond. After many years of research, the first efficacious CDK inhibitors have now been registered for clinical use in a defined segment of breast cancer. Research is underway to identify inhibitors with appropriate CDK-inhibitory profiles to recapitulate this success in other disease settings. Here we review the structural data that illustrates the interactions and properties that confer upon inhibitors affinity and/or selectivity towards different CDK family members. We conclude that where CDK inhibitors display selectivity, that selectivity derives from exploiting active site sequence peculiarities and/or from the capacity of the target CDK(s) to access conformations compatible with optimizing inhibitor-target interactions.

Publication metadata

Author(s): Martin MP, Endicott JA, Noble MEM

Publication type: Article

Publication status: Published

Journal: Essays in Biochemistry

Year: 2017

Volume: 61

Issue: 5

Pages: 439-452

Print publication date: 08/11/2017

Acceptance date: 25/09/2017

Date deposited: 03/10/2017

ISSN (print): 0071-1365

ISSN (electronic): 1744-1358

Publisher: Portland Press Ltd.


DOI: 10.1042/EBC20170040


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Funder referenceFunder name
C2115/A21421Cancer Research UK CRUK (closed comp)
MR/N009738/1Medical Research Council (MRC)