5EI4

First domain of human bromodomain BRD4 in complex with inhibitor 8-(5-Amino-1H-[1,2,4]triazol-3-ylsulfanylmethyl)-3-(4-chlorobenzyl)-7-ethyl-3,7-dihydropurine-2,6-dione

Summary for 5EI4

• Entry DOI: 10.2210/pdb5ei4/pdb
• Descriptor: Bromodomain-containing protein 4, 1,2-ETHANEDIOL, 8-[(3-azanyl-1~{H}-1,2,4-triazol-5-yl)sulfanylmethyl]-3-[(4-chlorophenyl)methyl]-7-ethyl-purine-2,6-dione, ... (4 entities in total)
• Functional Keywords: inhibitor, histone, epigenetic reader, bromodomain, brd4, brd4_bd1, brd4_bd1 29-o, transcription
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: O60885
• Total number of polymer chains: 1
• Total formula weight: 15594.33

Authors

Raux, B.,Rebuffet, E.,Betzi, S.,Morelli, X. (deposition date: 2015-10-29, release date: 2016-01-20, Last modification date: 2024-01-10)

Primary citation

Raux, B.,Voitovich, Y.,Derviaux, C.,Lugari, A.,Rebuffet, E.,Milhas, S.,Priet, S.,Roux, T.,Trinquet, E.,Guillemot, J.C.,Knapp, S.,Brunel, J.M.,Fedorov, A.Y.,Collette, Y.,Roche, P.,Betzi, S.,Combes, S.,Morelli, X.
Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins.
J.Med.Chem., 59:1634-1641, 2016

PubMed Abstract: A midthroughput screening follow-up program targeting the first bromodomain of the human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with an affinity in the low micromolar range yet exerts suitable unexpected selectivity in vitro against the other members of the bromodomain and extra-terminal domain (BET) family. A structure-based program pinpointed a role of the ZA loop, paving the way for the development of potent and selective BET-BRDi probes.

PubMed: 26735842
DOI: 10.1021/acs.jmedchem.5b01708

Experimental method

X-RAY DIFFRACTION (1.05 Å)