Lookup NU author(s): Dr Johanne Bentley,
Professor Jane Endicott,
Professor Martin Noble
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. The roles of four residues of the cyclin-dependent kinase active site in inhibitor selectivity were investigated by producing cyclin-dependent kinase 2 mutants bearing equivalent cyclin-dependent kinase 4 residues, namely F82H, L83V, H84D, and K89T. Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound. Use of the cyclin-dependent kinase 2-selective 6-cyclo-hexylmethoxy-2-(4′-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. The results indicate that certain residues that are not frequently considered in structure-aided kinase inhibitor design have an important role to play. © 2006 American Chemical Society.
Author(s): Pratt DJ, Bentley J, Jewsbury P, Boyle FT, Endicott JA, Noble MEM
Publication type: Article
Publication status: Published
Journal: Journal of Medicinal Chemistry
ISSN (print): 0022-2623
ISSN (electronic): 1520-4804
Publisher: American Chemical Society
PubMed id: 16942020
Altmetrics provided by Altmetric