4PCI

Crystal Structure of the first bromodomain of BRD4 in complex with B16

Summary for 4PCI

• Entry DOI: 10.2210/pdb4pci/pdb
• Related: 4PCE
• Descriptor: Bromodomain-containing protein 4, (4S)-1-methyl-4-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: transcription-transcription inhibitor complex, transcription/transcription inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: O60885
• Total number of polymer chains: 1
• Total formula weight: 15413.76

Authors

Dong, J.,Caflisch, A. (deposition date: 2014-04-15, release date: 2014-05-14, Last modification date: 2023-09-27)

Primary citation

Zhao, H.,Gartenmann, L.,Dong, J.,Spiliotopoulos, D.,Caflisch, A.
Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking.
Bioorg.Med.Chem.Lett., 24:2493-2496, 2014

PubMed 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.

PubMed: 24767840
DOI: 10.1016/j.bmcl.2014.04.017

Experimental method

X-RAY DIFFRACTION (1.25 Å)