R.M Angell
Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes
Angell, R.M; Angell, T.D; Bamborough, P; Bamford, M.J; Chung, C-W; Cockerill, G.S; Flack, S.S; Jones, K.L; Laine, D.I; Longstaff, T; Ludbrook, S; Pearson, R; Smith, K.J; Smee, P.A; Somers, D.O; Walker, A.L
Authors
T.D Angell
P Bamborough
M.J Bamford
C-W Chung
G.S Cockerill
S.S Flack
K.L Jones
D.I Laine
T Longstaff
S Ludbrook
R Pearson
K.J Smith
P.A Smee
D.O Somers
A.L Walker
Abstract
The biphenyl amides (BPAs) are a series of p38α MAP kinase inhibitors. Compounds are able to bind to the kinase in either the DFG-in or DFG-out conformation, depending on substituents. X-ray, binding, kinetic and cellular data are shown, providing the most detailed comparison to date between potent compounds from the same chemical series that bind to different p38α conformations. DFG-out-binding compounds could be made more potent than DFG-in-binding compounds by increasing their size. Unexpectedly, compounds that bound to the DGF-out conformation showed diminished selectivity. The kinetics of binding to the isolated enzyme and the effects of compounds on cells were largely unaffected by the kinase conformation bound.
Citation
Angell, R., Angell, T., Bamborough, P., Bamford, M., Chung, C., Cockerill, G., …Walker, A. (2008). Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes. Bioorganic and Medicinal Chemistry Letters, 18(15), 4433-4437. https://doi.org/10.1016/j.bmcl.2008.06.028
Journal Article Type | Article |
---|---|
Publication Date | Jan 1, 2008 |
Deposit Date | Sep 27, 2013 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Print ISSN | 0960-894X |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 18 |
Issue | 15 |
Pages | 4433-4437 |
DOI | https://doi.org/10.1016/j.bmcl.2008.06.028 |
Keywords | p38 Kinase inhibitors, MAP kinase, biphenyl amide, protein kinase X-ray structure, binding mode, DFG-out, selectivity, kinetics |
You might also like
1,4-Benzodiazepines as inhibitors of respiratory syncytial virus
(2006)
Journal Article
Downloadable Citations
About Durham Research Online (DRO)
Administrator e-mail: dro.admin@durham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search