5CGP

Selective pharmacological inhibition of the CREB binding protein bromodomain regulates inflammatory cytokines in macrophages and RGS4 in neurons

5CGP の概要

• エントリーDOI: 10.2210/pdb5cgp/pdb
• 関連するPDBエントリー: 5CFW
• 分子名称: CREB-binding protein, 5-(3,5-dimethyl-1,2-oxazol-4-yl)-2-[2-(4-methoxyphenyl)ethyl]-1-[2-(morpholin-4-yl)ethyl]-1H-benzimidazole (3 entities in total)
• 機能のキーワード: inhibitor, complex, transcription-inhibitor complex, transcription/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: 1
• 化学式量合計: 14683.92

構造登録者

Chekler, E.L.,Jones, L.H. (登録日: 2015-07-09, 公開日: 2016-04-20, 最終更新日: 2023-09-27)

主引用文献

Chekler, E.L.,Pellegrino, J.A.,Lanz, T.A.,Denny, R.A.,Flick, A.C.,Coe, J.,Langille, J.,Basak, A.,Liu, S.,Stock, I.A.,Sahasrabudhe, P.,Bonin, P.D.,Lee, K.,Pletcher, M.T.,Jones, L.H.
Transcriptional Profiling of a Selective CREB Binding Protein Bromodomain Inhibitor Highlights Therapeutic Opportunities.
Chem.Biol., 22:1588-1596, 2015

PubMed Abstract: Bromodomains are involved in transcriptional regulation through the recognition of acetyl lysine modifications on diverse proteins. Selective pharmacological modulators of bromodomains are lacking, although the largely hydrophobic nature of the pocket makes these modules attractive targets for small-molecule inhibitors. This work describes the structure-based design of a highly selective inhibitor of the CREB binding protein (CBP) bromodomain and its use in cell-based transcriptional profiling experiments. The inhibitor downregulated a number of inflammatory genes in macrophages that were not affected by a selective BET bromodomain inhibitor. In addition, the CBP bromodomain inhibitor modulated the mRNA level of the regulator of G-protein signaling 4 (RGS4) gene in neurons, suggesting a potential therapeutic opportunity for CBP inhibitors in the treatment of neurological disorders.

PubMed: 26670081
DOI: 10.1016/j.chembiol.2015.10.013

実験手法

X-RAY DIFFRACTION (1.96 Å)