Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B.
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Embargo End Date
ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2015-03-12
Date Accepted
Abstract
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.
Citation
Journal of medicinal chemistry, 2015, 58 (5), pp. 2553 - 2559
Source Title
Publisher
AMER CHEMICAL SOC
ISSN
0022-2623
eISSN
1520-4804
Collections
Research Team
Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
Medicinal Chemistry 4 (including Analytical Chemistry)
Medicinal Chemistry 4 (including Analytical Chemistry)