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Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2 : structure−activity relationship, structural biology, and cellular activity

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journal contribution
posted on 24.10.2012, 08:55 by Paolo Innocenti, Kwai-Ming J. Cheung, Savade Solanki, Corine Mas-Droux, Fiona Rowan, Sharon Yeoh, Kathy Boxall, Maura Westlake, Lisa Pickard, Tara Hardy, Joanne E. Baxter, G. Wynne Aherne, Richard Bayliss, Andrew M. Fry, Swen Hoelder
We report herein a series of Nek2 inhibitors based on an aminopyridine scaffold. These compounds have been designed by combining key elements of two previously discovered chemical series. Structure based design led to aminopyridine (R)-21, a potent and selective inhibitor able to modulate Nek2 activity in cells.

Funding

We acknowledge NHS funding to the NIHR Biomedical Research Centre and funding from Cancer Research UK Programme Grant C309/A8274. A.M.F. acknowledges support from Cancer Research UK, The Wellcome Trust, and the Association for International Cancer Research. R.B. acknowledges support from Cancer Research UK (Grant C24461/A10285 and infrastructure support for Structural Biology at the ICR), a Royal Society Research Fellowship, and the Career Development Programme of the ICR.

History

Citation

Journal of Medicinal Chemistry, 2012, 55 (7), pp. 3228–3241

Version

AM (Accepted Manuscript)

Published in

Journal of Medicinal Chemistry

Publisher

American Chemical Society

issn

0022-2623

eissn

1520-4804

Copyright date

2012

Available date

24/10/2012

Publisher version

http://pubs.acs.org/doi/abs/10.1021/jm201683b

Language

eng