High-throughput screening and hit validation of extracellular-related kinase 5 (ERK5) inhibitors

Myers, S. M. et al. (2016) High-throughput screening and hit validation of extracellular-related kinase 5 (ERK5) inhibitors. ACS Combinatorial Science, 18(8), pp. 444-455. (doi:10.1021/acscombsci.5b00155) (PMID:27400250)

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Abstract

The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57 617 compounds. Four distinct chemical series were evident within the screening hits. Resynthesis and reassay of the hits demonstrated that one series did not return active compounds, whereas three series returned active hits. Structure–activity studies demonstrated that the 4-benzoylpyrrole-2-carboxamide pharmacophore had excellent potential for further development. The minimum kinase binding pharmacophore was identified, and key examples demonstrated good selectivity for ERK5 over p38α kinase.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leung, Professor Hing
Authors: Myers, S. M., Bawn, R. H., Bisset, L. C., Blackburn, T. J., Cottyn, B., Molyneux, L., Wong, A.-C., Cano, C., Clegg, W., Harrington, R. W., Leung, H., Rigoreau, L., Vidot, S., Golding, B. T., Griffin, R. J., Hammonds, T., Newell, D. R., and Hardcastle, I. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:ACS Combinatorial Science
Publisher:ACS Publications
ISSN:2156-8952
ISSN (Online):1470-8752
Published Online:11 July 2016

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