- Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors.
Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors.
Journal of medicinal chemistry (2015-07-15)
Emmanuel H Demont, Chun-wa Chung, Rebecca C Furze, Paola Grandi, Anne-Marie Michon, Chris Wellaway, Nathalie Barrett, Angela M Bridges, Peter D Craggs, Hawa Diallo, David P Dixon, Clement Douault, Amanda J Emmons, Emma J Jones, Bhumika V Karamshi, Kelly Locke, Darren J Mitchell, Bernadette H Mouzon, Rab K Prinjha, Andy D Roberts, Robert J Sheppard, Robert J Watson, Paul Bamborough
PMID26155854
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.
MATERIALS
Product Number
Brand
Product Description
Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Sigma-Aldrich
2-Mercaptoethanol, Molecular Biology, suitable for electrophoresis, suitable for cell culture, BioReagent, 99% (GC/titration)
Sigma-Aldrich
Sodium chloride, Molecular Biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
Sodium chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
Trizma® base, BioPerformance Certified, meets EP, USP testing specifications, suitable for cell culture, ≥99.9% (titration)