Journal ArticleDOI
Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors
Emmanuel Hubert Demont,Chun-wa Chung,Rebecca C. Furze,Paola Grandi,Anne-Marie Michon,Christopher Roland Wellaway,Nathalie Barrett,Angela Bridges,Peter D. Craggs,Hawa Diallo,David P. Dixon,Clement Douault,Amanda Emmons,Emma J. Jones,Bhumika Karamshi,Kelly Locke,Darren Jason Mitchell,Bernadette Mouzon,Rab K. Prinjha,Andrew D. Roberts,Robert J. Sheppard,Robert J. Watson,Paul Bamborough +22 more
TLDR
The discovery of a hit from a fragment-based targeted array is described, which produced the first known micromolar inhibitors of the ATAD2 bromodomain.Abstract:
Overexpression of ATAD2 (ATPase family, AAA domain containing 2) has been linked to disease severity and progression in a wide range of cancers, and is implicated in the regulation of several drivers of cancer growth. Little is known of the dependence of these effects upon the ATAD2 bromodomain, which has been categorized as among the least tractable of its class. The absence of any potent, selective inhibitors limits clear understanding of the therapeutic potential of the bromodomain. Here, we describe the discovery of a hit from a fragment-based targeted array. Optimization of this produced the first known micromolar inhibitors of the ATAD2 bromodomain.read more
Citations
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Journal ArticleDOI
Bromodomains: a new target class for drug development
TL;DR: The current state of BET inhibitor biology is reviewed, the next wave of bromodomain inhibitors with clinical potential in oncology and non-oncology indications are discussed, and the lessons learned from BET inhibitor programmes should affect efforts to develop drugs that target non-BET bRomodomains and other epigenetic readers.
Journal ArticleDOI
Bromodomain inhibitors and cancer therapy: From structures to applications.
TL;DR: The structures and mechanisms associated with Bromodomain and Extra-Terminal motif (BET) inhibitors and non-BET inhibitors, their current status of development, and their promising role as anti-cancer agents are described.
Journal ArticleDOI
Disrupting Acetyl-Lysine Recognition: Progress in the Development of Bromodomain Inhibitors
F. Anthony Romero,Alexander M. Taylor,Terry Crawford,Vickie Tsui,Alexandre Côté,Steven Magnuson +5 more
TL;DR: An update to the progress in identifying selective bromodomain inhibitors and their use as biological tools, as well as a perspective on the field are provided.
Journal ArticleDOI
Bromodomain biology and drug discovery.
Nilesh Zaware,Ming-Ming Zhou +1 more
TL;DR: The current understanding of bromodomain biology is highlighted, and the latest development of small-molecule inhibitors that target these protein domains as emerging therapies for cancer and inflammatory disorders are discussed.
Journal ArticleDOI
Chemical probes and inhibitors of bromodomains outside the BET family
TL;DR: Significant progress has been made in discovering inhibitors and chemical probes of bromodomains, epigenetic readers of lysine acetylation, and their applications in medicine and materials science.
References
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