TY  - JOUR
A1  - Wu, Qin
A1  - Heidenreich, David Jonas
A1  - Zhou, Stanley
A1  - Ackloo, Suzanne
A1  - Krämer, Andreas
A1  - Nakka, Kiran
A1  - Lima-Fernandes, Evelyne
A1  - Deblois, Genevieve
A1  - Duan, Shili
A1  - Vellanki, Ravi N.
A1  - Li, Fengling
A1  - Vedadi, Masoud
A1  - Dilworth, Jeffrey
A1  - Lupien, Mathieu
A1  - Brennan, Paul E.
A1  - Arrowsmith, Cheryl H.
A1  - Müller, Susanne
A1  - Fedorov, Oleg
A1  - Filippakopoulos, Panagis
A1  - Knapp, Stefan
T1  - A chemical toolbox for the study of bromodomains and epigenetic signaling
T2  - Nature Communications
N2  - Bromodomains (BRDs) are conserved protein interaction modules which recognize (read) acetyl-lysine modifications, however their role(s) in regulating cellular states and their potential as targets for the development of targeted treatment strategies is poorly understood. Here we present a set of 25 chemical probes, selective small molecule inhibitors, covering 29 human bromodomain targets. We comprehensively evaluate the selectivity of this probe-set using BROMOscan and demonstrate the utility of the set identifying roles of BRDs in cellular processes and potential translational applications. For instance, we discovered crosstalk between histone acetylation and the glycolytic pathway resulting in a vulnerability of breast cancer cell lines under conditions of glucose deprivation or GLUT1 inhibition to inhibition of BRPF2/3 BRDs. This chemical probe-set will serve as a resource for future applications in the discovery of new physiological roles of bromodomain proteins in normal and disease states, and as a toolset for bromodomain target validation.
KW  - Cancer
KW  - Cell biology
KW  - Chemical biology
KW  - Drug discovery
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50126
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-501264
SN  - 2041-1723
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 10
IS  - 1, Art. 1915
SP  - 1
EP  - 14
PB  - Nature Publishing Group UK
CY  - [London]
ER  -