Abstract:
:Bromodomains (BRDs) recognize acetyl-lysine modified histone tails mediating epigenetic processes. BRD4, a protein containing two bromodomains, has emerged as an attractive therapeutic target for several types of cancer as well as inflammatory diseases. Using a fragment-based in silico screening approach, we identified two small molecules that bind to the first bromodomain of BRD4 with low-micromolar affinity and favorable ligand efficiency (0.37 kcal/mol per non-hydrogen atom), selectively over other families of bromodomains. Notably, the hit rate of the fragment-based in silico approach is about 10% as only 24 putative inhibitors, from an initial library of about 9 million molecules, were tested in vitro.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Zhao H,Gartenmann L,Dong J,Spiliotopoulos D,Caflisch Adoi
10.1016/j.bmcl.2014.04.017subject
Has Abstractpub_date
2014-06-01 00:00:00pages
2493-6issue
11eissn
0960-894Xissn
1464-3405pii
S0960-894X(14)00353-9journal_volume
24pub_type
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