- 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
ABSTRAKT
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.
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Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
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Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
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Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
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Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
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Benzonase® Nuclease, ultrapure, ≥250 units/μL, ≥99% (SDS-PAGE), recombinant, expressed in E. coli, buffered aqueous glycerol solution, ultrapure grade