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

Autor:	Myers SM; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K., Bawn RH; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K., Bisset LC; Newcastle Cancer Centre, Northern Institute for Cancer Research, Medical School, Framlington Place, Newcastle University , Paul O'Gorman Building, Newcastle upon Tyne, NE2 4HH, U.K., Blackburn TJ; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K., Cottyn B; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K., Molyneux L; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K., Wong AC; Cancer Research Technology, Ltd., Discovery Laboratories, Wolfson Institute for Biomedical Research, The Cruciform Building, Gower Street, London, WC1E 6BT, U.K., Cano C; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K., Clegg W; School of Chemistry, Newcastle University , Bedson Building, Newcastle upon Tyne, NE1 7RU, U.K., Harrington RW; School of Chemistry, Newcastle University , Bedson Building, Newcastle upon Tyne, NE1 7RU, U.K., Leung H; The Beatson Institute for Cancer Research , Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, U.K., Rigoreau L; Cancer Research Technology, Ltd., Discovery Laboratories, Wolfson Institute for Biomedical Research, The Cruciform Building, Gower Street, London, WC1E 6BT, U.K., Vidot S; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K., Golding BT; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K., Griffin RJ; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K., Hammonds T; Cancer Research Technology, Ltd., Discovery Laboratories, Wolfson Institute for Biomedical Research, The Cruciform Building, Gower Street, London, WC1E 6BT, U.K., Newell DR; Newcastle Cancer Centre, Northern Institute for Cancer Research, Medical School, Framlington Place, Newcastle University , Paul O'Gorman Building, Newcastle upon Tyne, NE2 4HH, U.K., Hardcastle IR; Newcastle Cancer Centre, Northern Institute for Cancer Research and School of Chemistry, Bedson Building, Newcastle University , Newcastle upon Tyne, NE1 7RU, U.K.
Jazyk:	angličtina
Zdroj:	ACS combinatorial science [ACS Comb Sci] 2016 Aug 08; Vol. 18 (8), pp. 444-55. Date of Electronic Publication: 2016 Jul 20.
DOI:	10.1021/acscombsci.5b00155
Abstrakt:	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.
Databáze:	MEDLINE
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