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

Autor: Fernández-Montalván AE; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Berger M; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Kuropka B; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Koo SJ; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Badock V; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Weiske J; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Puetter V; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Holton SJ; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Stöckigt D; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Ter Laak A; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Centrella PA; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Clark MA; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Dumelin CE; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Sigel EA; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Soutter HH; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Troast DM; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Zhang Y; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Cuozzo JW; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Keefe AD; X-Chem Pharmaceuticals , Waltham, Massachusetts United States., Roche D; Edelris , Lyon, France., Rodeschini V; Edelris , Lyon, France., Chaikuad A; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Díaz-Sáez L; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Bennett JM; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Fedorov O; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Huber KVM; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom.; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom., Hübner J; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Weinmann H; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Hartung IV; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany., Gorjánácz M; Bayer AG , Pharmaceuticals, Drug Discovery, Berlin, Germany.
Jazyk: angličtina
Zdroj: ACS chemical biology [ACS Chem Biol] 2017 Nov 17; Vol. 12 (11), pp. 2730-2736. Date of Electronic Publication: 2017 Oct 24.
DOI: 10.1021/acschembio.7b00708
Abstrakt: 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.
Databáze: MEDLINE