5HM0

Crystal structure of the first bromodomain of human BRD4 bound to benzoisoxazoloazepine 3

Summary for 5HM0

• Entry DOI: 10.2210/pdb5hm0/pdb
• Descriptor: Bromodomain-containing protein 4, 6-(4-chlorophenyl)-1-methyl-4H-[1,2]oxazolo[5,4-d][2]benzazepine (3 entities in total)
• Functional Keywords: bromodomain, transcription
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: O60885
• Total number of polymer chains: 1
• Total formula weight: 15435.10

Authors

Jayaram, H.,Poy, F.,Setser, J.W.,Bellon, S.F. (deposition date: 2016-01-15, release date: 2016-02-10, Last modification date: 2023-09-27)

Primary citation

Albrecht, B.K.,Gehling, V.S.,Hewitt, M.C.,Vaswani, R.G.,Cote, A.,Leblanc, Y.,Nasveschuk, C.G.,Bellon, S.,Bergeron, L.,Campbell, R.,Cantone, N.,Cooper, M.R.,Cummings, R.T.,Jayaram, H.,Joshi, S.,Mertz, J.A.,Neiss, A.,Normant, E.,O'Meara, M.,Pardo, E.,Poy, F.,Sandy, P.,Supko, J.,Sims, R.J.,Harmange, J.C.,Taylor, A.M.,Audia, J.E.
Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials.
J.Med.Chem., 59:1330-1339, 2016

PubMed Abstract: In recent years, inhibition of the interaction between the bromodomain and extra-terminal domain (BET) family of chromatin adaptors and acetyl-lysine residues on chromatin has emerged as a promising approach to regulate the expression of important disease-relevant genes, including MYC, BCL-2, and NF-κB. Here we describe the identification and characterization of a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor that attenuates BET-dependent gene expression in vivo, demonstrates antitumor efficacy in an MV-4-11 mouse xenograft model, and is currently undergoing human clinical trials for hematological malignancies (CPI-0610).

PubMed: 26815195
DOI: 10.1021/acs.jmedchem.5b01882

Experimental method

X-RAY DIFFRACTION (1.395 Å)