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Synfacts 2020; 16(07): 0847
DOI: 10.1055/s-0040-1707877
Chemistry in Medicine and Biology
© Georg Thieme Verlag Stuttgart · New York

Selectively Binding a Bromodomain

Contributor(s):
Dirk Trauner
,
Martin Reynders
Prinjha RK. * Dawson MA. * et al. GlaxoSmithKline Medicines Research Centre, Stevenage, UK; Peter MacCallum Cancer Centre, Melbourne, and University of Melbourne, Australia
Selective Targeting of BD1 and BD2 of the BET Proteins in Cancer and Immunoinflammation.

Science 2020;
368: 387-394
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Publication History

Publication Date:
17 June 2020 (online)

 
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Key words

BET inhibitors - bromodomain - epigenetics - BRD4 - cancer

Significance

The BET (bromo- and extraterminal) family of proteins are epigenetic readers, modulate gene expression, and are attractive anticancer targets. The human BET proteins contain two highly homologous bromodomains, BD1 and BD2, equally bound by classical inhibitors. Selective inhibitors enable studies on the individual functions of BD1 and BD2.


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Comment

Prinjha, Dawson, and co-workers developed very selective inhibitors for BD1 (iBET-BD1) and BD2 (iBET-BD2), complementing recently developed ABBV-744 (Nature 2020, 578, 306). They show that BD1 inhibition replicates the effect of pan-BET inhibitors in cancer models, whereas BD2 inhibition is more effective in models of immunoinflammation.


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