5HLS

Crystal structure of the first bromodomain of human BRD4 bound to CPI-0610

5HLS の概要

• エントリーDOI: 10.2210/pdb5hls/pdb
• 分子名称: Bromodomain-containing protein 4, CPI-0610 (3 entities in total)
• 機能のキーワード: bromodomain, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: O60885
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15492.15

構造登録者

Jayaram, H.,Poy, F.,Setser, J.W.,Bellon, S.F. (登録日: 2016-01-15, 公開日: 2016-02-10, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.182 Å)