A novel pan-selective bromodomain inhibitor for epigenetic drug design.

For a long time, the development of bromodomain (BD) inhibitors (BDi) was almost exclusively related to the BET family. More recently, BDi for BDs outside the BET family have also been developed. Here we present a novel pan-BDi with micromolar affinities to various BDs, and nanomolar affinities to representatives of BD families I, II (Bromodomain and Extra-Terminal Domain (BET) family), III, and IV. The inhibitor shows a broad activity profile with nanomolar growth inhibition (GI50) values on various cancer cell lines. Subsequently, we were able to control the selectivity of the inhibitor by simple modifications and turned it into a highly selective BRD9 inhibitor.

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Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stefan Guenther, Manfred Jung and Oliver Einsle has patent #Compounds for use as bromodomain inhibitors/US20160068485A1 licensed to Albert Ludwigs Universitaet Freiburg. Stefan Guenther, Martin Huegle, Pierre-Michel Regenass, Mehrosh Pervaiz, Robin Warstat, Bernhard Breit and Oliver Einsle has patent #EP 18 215 794.1, „Novel bromodomain inhibitors” pending to Albert Ludwigs Universitaet Freiburg.