6E4A

Crystal structure of human BRD4(1) in complex with CN750

Summary for 6E4A

• Entry DOI: 10.2210/pdb6e4a/pdb
• Descriptor: Bromodomain-containing protein 4, 5-(4-{[(3-chlorophenyl)methyl]amino}-2-{4-[2-(dimethylamino)ethyl]piperazin-1-yl}quinazolin-6-yl)-1-methylpyridin-2(1H)-one, GLYCEROL, ... (4 entities in total)
• Functional Keywords: brd4(bd1), protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 31999.64

Authors

Fontano, E.,White, A.,Lakshminarasimhan, D.,Suto, R.K. (deposition date: 2018-07-17, release date: 2018-09-12, Last modification date: 2024-03-13)

Primary citation

Yang, S.M.,Urban, D.J.,Yoshioka, M.,Strovel, J.W.,Fletcher, S.,Wang, A.Q.,Xu, X.,Shah, P.,Hu, X.,Hall, M.D.,Jadhav, A.,Maloney, D.J.
Discovery and lead identification of quinazoline-based BRD4 inhibitors.
Bioorg. Med. Chem. Lett., 28:3483-3488, 2018

PubMed Abstract: A new series of quinazoline-based analogs as potent bromodomain-containing protein 4 (BRD4) inhibitors is described. The structure-activity relationships on 2- and 4-position of quinazoline ring, and the substitution at 6-position that mimic the acetylated lysine are discussed. A co-crystallized structure of 48 (CN750) with BRD4 (BD1) including key inhibitor-protein interactions is also highlighted. Together with preliminary rodent pharmacokinetic results, a new lead (65, CN427) is identified which is suitable for further lead optimization.

PubMed: 30268702
DOI: 10.1016/j.bmcl.2018.08.039

Experimental method

X-RAY DIFFRACTION (1.26 Å)