A Chemical Probe for the ATAD2 Bromodomain
Accepted version
Peer-reviewed
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Abstract
ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.
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Keywords
3404 Medicinal and Biomolecular Chemistry, 34 Chemical Sciences, Cancer
Journal Title
Angewandte Chemie
Conference Name
Journal ISSN
0044-8249
1521-3757
1521-3757
Volume Title
128
Publisher
Wiley
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Sponsorship
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Cancer Research Uk (None)
A.J.B., K.H.C., S.R. and T.K. acknowledge grants from Wellcome Trust (092096), Cancer Research UK (C6946/A14492, RG17001), and BBSRC (RG69031).