High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors

Myers, Stephanie, Bawn, Ruth H., Bisset, Louise C., Blackburn, Timothy J., Cottyn, Betty, Molyneux, Lauren, Wong, Ai-Ching, Cano, Celine, Clegg, William, Harrington, Ross. W., Leung, Hing, Rigoreau, Laurent, Vidot, Sandrine, Golding, Bernard T., Griffin, Roger J., Hammonds, Tim, Newell, David R. and Hardcastle, Ian R. (2016) High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors. ACS Combinatorial Science, 18 (8). pp. 444-455. ISSN 2156-8952

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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: Article
Subjects: Sciences > Chemistry
Sciences > Pharmacy and Pharmacology
Divisions: Faculty of Health Sciences and Wellbeing
Depositing User: Stephanie Myers
Date Deposited: 09 May 2018 10:07
Last Modified: 09 May 2018 10:07
URI: http://sure.sunderland.ac.uk/id/eprint/9285

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