5HCL

Crystal Structure of the first bromodomain of BRD4 in complex with DMA

5HCL の概要

• エントリーDOI: 10.2210/pdb5hcl/pdb
• 分子名称: Bromodomain-containing protein 4, ~{N},~{N}-dimethylethanamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: transcription-transcription inhibitor complex, transcription/transcription inhibitor
• 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: 15248.57

構造登録者

Dong, J.,Weber, F.E.,Caflisch, A. (登録日: 2016-01-04, 公開日: 2017-01-25, 最終更新日: 2024-01-10)

主引用文献

Ghayor, C.,Gjoksi, B.,Dong, J.,Siegenthaler, B.,Caflisch, A.,Weber, F.E.
N,N Dimethylacetamide a drug excipient that acts as bromodomain ligand for osteoporosis treatment.
Sci Rep, 7:42108-42108, 2017

PubMed Abstract: N,N-Dimethylacetamide (DMA) is a water-miscible solvent, FDA approved as excipient and therefore widely used as drug-delivery vehicle. As such, DMA should be devoid of any bioactivity. Here we report that DMA is epigenetically active since it binds bromodomains and inhibits osteoclastogenesis and inflammation. Moreover, DMA enhances bone regeneration in vivo. Therefore, our in vivo and in vitro data reveal DMA's potential as an anti-osteoporotic agent via the inhibition of osteoclast mediated bone resorption and enhanced bone regeneration. Our results highlight the potential therapeutic benefits of DMA and the need for reconsideration of previous reports where DMA was used as an 'inactive' drug-delivery vehicle.

PubMed: 28176838
DOI: 10.1038/srep42108

実験手法

X-RAY DIFFRACTION (1.5 Å)