@article{bibcite_489,
  keywords = {Humans, Molecular Docking Simulation, Structure-Activity Relationship, Ligands, Molecular Structure, Drug Discovery, Chromosomal Proteins, Non-Histone, Dose-Response Relationship, Drug},
  author = {D. Spiliotopoulos and E.-C. Wamhoff and G. Lolli and C. Rademacher and A. Caflisch},
  title = {Discovery of BAZ2A bromodomain ligands},
  abstract = {<p>The bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) is implicated in aggressive prostate cancer. The BAZ2A bromodomain is a challenging target because of the shallow pocket of its natural ligand, the acetylated side chain of lysine. Here, we report the successful screening of a library of nearly 1500 small molecules by high-throughput docking and force field-based binding-energy evaluation. For seven of the 20 molecules selected <i>in silico</i>, evidence of binding to the BAZ2A bromodomain is provided by ligand-observed NMR spectroscopy. Two of these compounds show a favorable ligand efficiency of 0.42~kcal/mol per non-hydrogen atom in a competition-binding assay. The crystal structures of the BAZ2A bromodomain in complex with four fragment hits validate the predicted binding modes. The binding modes of compounds 1 and 3 are compatible with ligand growing for optimization of affinity for BAZ2A and selectivity against the close homologue BAZ2B.</p>},
  year = {2017},
  journal = {European Journal of Medicinal Chemistry},
  volume = {139},
  chapter = {564},
  pages = {564-572},
  month = {2017 Oct 20},
  issn = {1768-3254},
  doi = {10.1016/j.ejmech.2017.08.028},
  language = {eng},
}