Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B.
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Date
2015-03-12Author
Drouin, L
McGrath, S
Vidler, LR
Chaikuad, A
Monteiro, O
Tallant, C
Philpott, M
Rogers, C
Fedorov, O
Liu, M
Akhtar, W
Hayes, A
Raynaud, F
Müller, S
Knapp, S
Hoelder, S
Type
Journal Article
Metadata
Show full item recordAbstract
The bromodomain containing proteins BAZ2A/B play essential roles in chromatin remodeling and regulation of noncoding RNAs. We present the structure based discovery of a potent, selective, and cell active inhibitor 13 (BAZ2-ICR) of the BAZ2A/B bromodomains through rapid optimization of a weakly potent starting point. A key feature of the presented inhibitors is an intramolecular aromatic stacking interaction that efficiently occupies the shallow bromodomain pockets. 13 represents an excellent chemical probe for functional studies of the BAZ2 bromodomains in vitro and in vivo.
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Subject
Microsomes
Animals
Mice
Triazoles
Chromosomal Proteins, Non-Histone
Molecular Probes
Molecular Structure
Structure-Activity Relationship
Drug Design
Models, Molecular
Research team
Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
Medicinal Chemistry 4 (including Analytical Chemistry)
Language
eng
License start date
2015-03
Citation
Journal of medicinal chemistry, 2015, 58 (5), pp. 2553 - 2559
Publisher
AMER CHEMICAL SOC