5I86

Crystal structure of the bromodomain of human CREBBP bound to the benzodiazepinone G02778174

5I86 の概要

• エントリーDOI: 10.2210/pdb5i86/pdb
• 関連するPDBエントリー: 5I83 5I89
• 分子名称: CREB-binding protein, 1,2-ETHANEDIOL, THIOCYANATE ION, ... (5 entities in total)
• 機能のキーワード: bromodomain inhibitor, protein binding-inhibitor complex, protein binding/inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: Q92793
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28784.96

構造登録者

Jayaram, H.,Poy, F.,Setser, J.W.,Bellon, S.F. (登録日: 2016-02-18, 公開日: 2016-04-20, 最終更新日: 2023-09-27)

主引用文献

Taylor, A.M.,Cote, A.,Hewitt, M.C.,Pastor, R.,Leblanc, Y.,Nasveschuk, C.G.,Romero, F.A.,Crawford, T.D.,Cantone, N.,Jayaram, H.,Setser, J.,Murray, J.,Beresini, M.H.,de Leon Boenig, G.,Chen, Z.,Conery, A.R.,Cummings, R.T.,Dakin, L.A.,Flynn, E.M.,Huang, O.W.,Kaufman, S.,Keller, P.J.,Kiefer, J.R.,Lai, T.,Li, Y.,Liao, J.,Liu, W.,Lu, H.,Pardo, E.,Tsui, V.,Wang, J.,Wang, Y.,Xu, Z.,Yan, F.,Yu, D.,Zawadzke, L.,Zhu, X.,Zhu, X.,Sims, R.J.,Cochran, A.G.,Bellon, S.,Audia, J.E.,Magnuson, S.,Albrecht, B.K.
Fragment-Based Discovery of a Selective and Cell-Active Benzodiazepinone CBP/EP300 Bromodomain Inhibitor (CPI-637).
Acs Med.Chem.Lett., 7:531-536, 2016

PubMed Abstract: CBP and EP300 are highly homologous, bromodomain-containing transcription coactivators involved in numerous cellular pathways relevant to oncology. As part of our effort to explore the potential therapeutic implications of selectively targeting bromodomains, we set out to identify a CBP/EP300 bromodomain inhibitor that was potent both in vitro and in cellular target engagement assays and was selective over the other members of the bromodomain family. Reported here is a series of cell-potent and selective probes of the CBP/EP300 bromodomains, derived from the fragment screening hit 4-methyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-one.

PubMed: 27190605
DOI: 10.1021/acsmedchemlett.6b00075

実験手法

X-RAY DIFFRACTION (1.05 Å)