4 research outputs found
Human Pleckstrin Homology domain Interacting Protein (PHIP); A Target Enabling Package
<p>SGC Oxford has expressed, purified and crystallized the second bromodomain of PHIP as part of the probe programme. Fragment screening and X-ray crystallography identified binders, some of which optimised to uM affinity. However, molecules with probe properties were not obtained. Consequently it has been decided to put the information generated into the public domain.</p
Human Pleckstrin Homology domain Interacting Protein (PHIP); A Target Enabling Package
<p>SGC Oxford has expressed, purified and crystallized the second bromodomain of PHIP as part of the probe programme. Fragment screening and X-ray crystallography identified binders, some of which optimised to uM affinity. However, molecules with probe properties were not obtained. Consequently it has been decided to put the information generated into the public domain.</p
Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF
TRIM24 is a transcriptional regulator
as well as an E3 ubiquitin
ligase. It is overexpressed in diverse tumors, and high expression
levels have been linked to poor prognosis in breast cancer patients.
TRIM24 contains a PHD/bromodomain offering the opportunity to develop
protein interaction inhibitors that target this protein interaction
module. Here we identified potent acetyl-lysine mimetic benzimidazolones
TRIM24 bromodomain inhibitors. The best compound of this series is
a selective BRPF1B/TRIM24 dual inhibitor that bound with a <i>K</i><sub>D</sub> of 137 and 222 nM, respectively, but exerted
good selectivity over other bromodomains. Cellular activity of the
inhibitor was demonstrated using FRAP assays as well as cell viability
data
Structure Enabled Design of BAZ2-ICR, A Chemical Probe Targeting the Bromodomains of BAZ2A and BAZ2B
The bromodomain containing proteins
BAZ2A/B play essential roles
in chromatin remodeling and regulation of noncoding RNAs. We present
the structure based discovery of a potent, selective, and cell active
inhibitor <b>13</b> (BAZ2-ICR) of the BAZ2A/B bromodomains through
rapid optimization of a weakly potent starting point. A key feature
of the presented inhibitors is an intramolecular aromatic stacking
interaction that efficiently occupies the shallow bromodomain pockets. <b>13</b> represents an excellent chemical probe for functional studies
of the BAZ2 bromodomains in vitro and in vivo