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
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.
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.
