Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2 : structure−activity relationship, structural biology, and cellular activity
journal contribution
posted on 2012-10-24, 08:55 authored 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 HoelderWe 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. 3228–3241Version
- AM (Accepted Manuscript)
Published in
Journal of Medicinal ChemistryPublisher
American Chemical Societyissn
0022-2623eissn
1520-4804Copyright date
2012Available date
2012-10-24Publisher DOI
Publisher version
http://pubs.acs.org/doi/abs/10.1021/jm201683bLanguage
engAdministrator link
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