Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action

[Image: see text] ATAD2 (ANCCA) is an epigenetic regulator and transcriptional cofactor, whose overexpression has been linked to the progress of various cancer types. Here, we report a DNA-encoded library screen leading to the discovery of BAY-850, a potent and isoform selective inhibitor that speci...

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Autores principales: Fernández-Montalván, Amaury E., Berger, Markus, Kuropka, Benno, Koo, Seong Joo, Badock, Volker, Weiske, Joerg, Puetter, Vera, Holton, Simon J., Stöckigt, Detlef, ter Laak, Antonius, Centrella, Paolo A., Clark, Matthew A., Dumelin, Christoph E., Sigel, Eric A., Soutter, Holly H., Troast, Dawn M., Zhang, Ying, Cuozzo, John W., Keefe, Anthony D., Roche, Didier, Rodeschini, Vincent, Chaikuad, Apirat, Díaz-Sáez, Laura, Bennett, James M., Fedorov, Oleg, Huber, Kilian V. M., Hübner, Jan, Weinmann, Hilmar, Hartung, Ingo V., Gorjánácz, Mátyás
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218015/
https://www.ncbi.nlm.nih.gov/pubmed/29043777
http://dx.doi.org/10.1021/acschembio.7b00708
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author Fernández-Montalván, Amaury E.
Berger, Markus
Kuropka, Benno
Koo, Seong Joo
Badock, Volker
Weiske, Joerg
Puetter, Vera
Holton, Simon J.
Stöckigt, Detlef
ter Laak, Antonius
Centrella, Paolo A.
Clark, Matthew A.
Dumelin, Christoph E.
Sigel, Eric A.
Soutter, Holly H.
Troast, Dawn M.
Zhang, Ying
Cuozzo, John W.
Keefe, Anthony D.
Roche, Didier
Rodeschini, Vincent
Chaikuad, Apirat
Díaz-Sáez, Laura
Bennett, James M.
Fedorov, Oleg
Huber, Kilian V. M.
Hübner, Jan
Weinmann, Hilmar
Hartung, Ingo V.
Gorjánácz, Mátyás
author_facet Fernández-Montalván, Amaury E.
Berger, Markus
Kuropka, Benno
Koo, Seong Joo
Badock, Volker
Weiske, Joerg
Puetter, Vera
Holton, Simon J.
Stöckigt, Detlef
ter Laak, Antonius
Centrella, Paolo A.
Clark, Matthew A.
Dumelin, Christoph E.
Sigel, Eric A.
Soutter, Holly H.
Troast, Dawn M.
Zhang, Ying
Cuozzo, John W.
Keefe, Anthony D.
Roche, Didier
Rodeschini, Vincent
Chaikuad, Apirat
Díaz-Sáez, Laura
Bennett, James M.
Fedorov, Oleg
Huber, Kilian V. M.
Hübner, Jan
Weinmann, Hilmar
Hartung, Ingo V.
Gorjánácz, Mátyás
author_sort Fernández-Montalván, Amaury E.
collection PubMed
description [Image: see text] ATAD2 (ANCCA) is an epigenetic regulator and transcriptional cofactor, whose overexpression has been linked to the progress of various cancer types. Here, we report a DNA-encoded library screen leading to the discovery of BAY-850, a potent and isoform selective inhibitor that specifically induces ATAD2 bromodomain dimerization and prevents interactions with acetylated histones in vitro, as well as with chromatin in cells. These features qualify BAY-850 as a chemical probe to explore ATAD2 biology.
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spelling pubmed-62180152018-11-05 Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action Fernández-Montalván, Amaury E. Berger, Markus Kuropka, Benno Koo, Seong Joo Badock, Volker Weiske, Joerg Puetter, Vera Holton, Simon J. Stöckigt, Detlef ter Laak, Antonius Centrella, Paolo A. Clark, Matthew A. Dumelin, Christoph E. Sigel, Eric A. Soutter, Holly H. Troast, Dawn M. Zhang, Ying Cuozzo, John W. Keefe, Anthony D. Roche, Didier Rodeschini, Vincent Chaikuad, Apirat Díaz-Sáez, Laura Bennett, James M. Fedorov, Oleg Huber, Kilian V. M. Hübner, Jan Weinmann, Hilmar Hartung, Ingo V. Gorjánácz, Mátyás ACS Chem Biol [Image: see text] ATAD2 (ANCCA) is an epigenetic regulator and transcriptional cofactor, whose overexpression has been linked to the progress of various cancer types. Here, we report a DNA-encoded library screen leading to the discovery of BAY-850, a potent and isoform selective inhibitor that specifically induces ATAD2 bromodomain dimerization and prevents interactions with acetylated histones in vitro, as well as with chromatin in cells. These features qualify BAY-850 as a chemical probe to explore ATAD2 biology. American Chemical Society 2017-10-18 2017-11-17 /pmc/articles/PMC6218015/ /pubmed/29043777 http://dx.doi.org/10.1021/acschembio.7b00708 Text en Copyright © 2017 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Fernández-Montalván, Amaury E.
Berger, Markus
Kuropka, Benno
Koo, Seong Joo
Badock, Volker
Weiske, Joerg
Puetter, Vera
Holton, Simon J.
Stöckigt, Detlef
ter Laak, Antonius
Centrella, Paolo A.
Clark, Matthew A.
Dumelin, Christoph E.
Sigel, Eric A.
Soutter, Holly H.
Troast, Dawn M.
Zhang, Ying
Cuozzo, John W.
Keefe, Anthony D.
Roche, Didier
Rodeschini, Vincent
Chaikuad, Apirat
Díaz-Sáez, Laura
Bennett, James M.
Fedorov, Oleg
Huber, Kilian V. M.
Hübner, Jan
Weinmann, Hilmar
Hartung, Ingo V.
Gorjánácz, Mátyás
Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action
title Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action
title_full Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action
title_fullStr Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action
title_full_unstemmed Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action
title_short Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action
title_sort isoform-selective atad2 chemical probe with novel chemical structure and unusual mode of action
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218015/
https://www.ncbi.nlm.nih.gov/pubmed/29043777
http://dx.doi.org/10.1021/acschembio.7b00708
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