8PXM

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH (1R,1'R)-7,7'-(pentane-1,5-diylbis(oxy))bis(1,3-dimethyl-1,3-dihydro-2H-benzo[d]azepin-2-one)

Summary for 8PXM

• Entry DOI: 10.2210/pdb8pxm/pdb
• Descriptor: Bromodomain-containing protein 4, (1R)-7-[5-[[(1R)-1,3-dimethyl-2-oxidanylidene-1H-3-benzazepin-7-yl]oxy]pentoxy]-1,3-dimethyl-1H-3-benzazepin-2-one, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: inhibitor, histone, epigenetic reader, bromodomain, brd4, bromodomain containing protein 4, antagonist, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 30735.42

Authors

Chung, C.W. (deposition date: 2023-07-23, release date: 2023-10-04)

Primary citation

Bamborough, P.,Chung, C.W.,Goodwin, N.C.,Mitchell, D.J.,Neipp, C.E.,Phillipou, A.,Preston, A.,Prinjha, R.K.,Soden, P.E.,Watson, R.J.,Demont, E.H.
Design and Characterization of 1,3-Dihydro-2 H -benzo[ d ]azepin-2-ones as Rule-of-5 Compliant Bivalent BET Inhibitors.
Acs Med.Chem.Lett., 14:1231-1236, 2023

PubMed Abstract: The 1,3-dihydro-2-benzo[]azepin-2-ones are potent and ligand-efficient pan-BET bromodomain inhibitors. Here we describe the extension of this template to exploit a bivalent mode of action, binding simultaneously to both bromodomains. Initially the linker length and attachment vectors compatible with bivalent binding were explored, leading to the discovery of exceptionally potent bivalent BET inhibitors within druglike rule-of-5 space.

PubMed: 37736196
DOI: 10.1021/acsmedchemlett.3c00242

Experimental method

X-RAY DIFFRACTION (2.378 Å)