Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10592131 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
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 (0.37Â 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.
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Authors
Hongtao Zhao, Lisa Gartenmann, Jing Dong, Dimitrios Spiliotopoulos, Amedeo Caflisch,