| Literature DB >> 24504667 |
Eric Jnoff1, Claudia Albrecht, John J Barker, Oliver Barker, Edward Beaumont, Steven Bromidge, Frederick Brookfield, Mark Brooks, Christian Bubert, Tom Ceska, Vincent Corden, Graham Dawson, Stephanie Duclos, Tara Fryatt, Christophe Genicot, Emilie Jigorel, Jason Kwong, Rosemary Maghames, Innocent Mushi, Richard Pike, Zara A Sands, Myron A Smith, Christopher C Stimson, Jean-Philippe Courade.
Abstract
An X-ray crystal structure of Kelch-like ECH-associated protein (Keap1) co-crystallised with (1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-carbonyl]cyclohexane-1-carboxylic acid (compound (S,R,S)-1 a) was obtained. This X-ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)-1 a, as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.Entities:
Keywords: CNS; Keap1; Nrf2; co-crystal structures; docking; structure-activity relationships
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Year: 2014 PMID： 24504667 DOI： 10.1002/cmdc.201300525
Source DB: PubMed Journal: ChemMedChem ISSN： 1860-7179 Impact factor: 3.466