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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Detalles Bibliográficos
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
Descripción
Sumario:[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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