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ID: ALA3585343

Journal: J Med Chem

Title: Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors.

Authors: Demont EH, Chung CW, Furze RC, Grandi P, Michon AM, Wellaway C, Barrett N, Bridges AM, Craggs PD, Diallo H, Dixon DP, Douault C, Emmons AJ, Jones EJ, Karamshi BV, Locke K, Mitchell DJ, Mouzon BH, Prinjha RK, Roberts AD, Sheppard RJ, Watson RJ, Bamborough P.

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.

CiteXplore: 26155854

DOI: 10.1021/acs.jmedchem.5b00772