2. Academic Validation
  3. Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action

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

  • ACS Chem Biol. 2017 Nov 17;12(11):2730-2736. doi: 10.1021/acschembio.7b00708.
Amaury E Fernández-Montalván 1,  Markus Berger 1,  Benno Kuropka 1,  Seong Joo Koo 1,  Volker Badock 1,  Joerg Weiske 1,  Vera Puetter 1,  Simon J Holton 1,  Detlef Stöckigt 1,  Antonius Ter Laak 1,  Paolo A Centrella 2,  Matthew A Clark 2,  Christoph E Dumelin 2,  Eric A Sigel 2,  Holly H Soutter 2,  Dawn M Troast 2,  Ying Zhang 2,  John W Cuozzo 2,  Anthony D Keefe 2,  Didier Roche 3,  Vincent Rodeschini 3,  Apirat Chaikuad 4 5,  Laura Díaz-Sáez 4 5,  James M Bennett 4 5,  Oleg Fedorov 4 5,  Kilian V M Huber 4 5,  Jan Hübner 1,  Hilmar Weinmann 1,  Ingo V Hartung 1,  Mátyás Gorjánácz 1
Affiliations

Affiliations

  • 1 Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany.
  • 2 X-Chem Pharmaceuticals , Waltham, Massachusetts United States.
  • 3 Edelris , Lyon, France.
  • 4 Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.
  • 5 Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.
PMID: 29043777 DOI: 10.1021/acschembio.7b00708
Abstract

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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