7O18

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH I-BET282

This is a non-PDB format compatible entry.

Summary for 7O18

• Entry DOI: 10.2210/pdb7o18/pdb
• Descriptor: Bromodomain-containing protein 4, 1,2-ETHANEDIOL, (R)-4-(8-methoxy-1-(1-methoxypropan-2-yl)-2-(tetrahydro-2H-pyran-4-yl)-1H-imidazo[4,5-c]quinolin-7-yl)-3,5-dimethylisoxazole, ... (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: 1
• Total formula weight: 15674.05

Authors

Chung, C. (deposition date: 2021-03-28, release date: 2021-10-13, Last modification date: 2024-05-01)

Primary citation

Jones, K.L.,Beaumont, D.M.,Bernard, S.G.,Bit, R.A.,Campbell, S.P.,Chung, C.W.,Cutler, L.,Demont, E.H.,Dennis, K.,Gordon, L.,Gray, J.R.,Haase, M.V.,Lewis, A.J.,McCleary, S.,Mitchell, D.J.,Moore, S.M.,Parr, N.,Robb, O.J.,Smithers, N.,Soden, P.E.,Suckling, C.J.,Taylor, S.,Walker, A.L.,Watson, R.J.,Prinjha, R.K.
Discovery of a Novel Bromodomain and Extra Terminal Domain (BET) Protein Inhibitor, I-BET282E, Suitable for Clinical Progression.
J.Med.Chem., 64:12200-12227, 2021

PubMed Abstract: The functions of the bromodomain and extra terminal (BET) family of proteins have been implicated in a wide range of diseases, particularly in the oncology and immuno-inflammatory areas, and several inhibitors are under investigation in the clinic. To mitigate the risk of attrition of these compounds due to structurally related toxicity findings, additional molecules from distinct chemical series were required. Here we describe the structure- and property-based optimization of the tool molecule I-BET151 toward I-BET282E, a molecule with properties suitable for progression into clinical studies.

PubMed: 34387088
DOI: 10.1021/acs.jmedchem.1c00855

Experimental method

X-RAY DIFFRACTION (1.7 Å)