@article{bibcite_309,
  keywords = {Models, Molecular, Humans, Structure-Activity Relationship, Molecular Structure, Nuclear Proteins, Drug Discovery, Small Molecule Libraries, High-Throughput Screening Assays, Dose-Response Relationship, Drug, Transcription Factors},
  author = {H. Zhao and L. Gartenmann and J. Dong and D. Spiliotopoulos and A. Caflisch},
  title = {Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking},
  abstract = {<p>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 <i>in silico</i> 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 <i>in silico</i> approach is about 10\% as only 24 putative inhibitors, from an initial library of about 9 million molecules, were tested <i>in vitro</i>.</p>},
  year = {2014},
  journal = {Bioorganic \& Medicinal Chemistry Letters},
  volume = {24},
  pages = {2493-2496},
  month = {2014 Jun 1},
  issn = {1464-3405},
  doi = {10.1016/j.bmcl.2014.04.017},
  language = {eng},
}