| Literature DB >> 27400250 |
Stephanie M Myers1, Ruth H Bawn1, Louise C Bisset2, Timothy J Blackburn1, Betty Cottyn1, Lauren Molyneux1, Ai-Ching Wong3, Celine Cano1, William Clegg4, Ross W Harrington4, Hing Leung5, Laurent Rigoreau3, Sandrine Vidot1, Bernard T Golding1, Roger J Griffin1, Tim Hammonds3, David R Newell2, Ian R Hardcastle1.
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.Entities:
Keywords: cancer therapy; extracellular-related kinase 5 (ERK5); high-throughput screening; library; p38α kinase; structure−activity studies
Mesh：
Substances：
Year: 2016 PMID： 27400250 DOI： 10.1021/acscombsci.5b00155
Source DB: PubMed Journal: ACS Comb Sci ISSN： 2156-8944 Impact factor: 3.784