8YMG

BRD4-BD1 in complex with 7-[4-chloro-1-(tetrahydropyran-4-ylmethyl)imidazol-2-yl]-5-methyl-2-{[(2R)-2-methyl-4-methylsulfonyl-piperazin-1-yl]methyl}furo[3,2-c]pyridin-4-one

これはPDB形式変換不可エントリーです。

8YMG の概要

• エントリーDOI: 10.2210/pdb8ymg/pdb
• 分子名称: Bromodomain-containing protein 4, 7-[4-chloro-1-(tetrahydropyran-4-ylmethyl)imidazol-2-yl]-5-methyl-2-{[(2R)-2-methyl-4-methylsulfonyl-piperazin-1-yl]methyl}furo[3,2-c]pyridin-4-one (3 entities in total)
• 機能のキーワード: brd4, epigenetic, signaling protein-inhibitor complex, signaling protein/inhibitor, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15694.49

構造登録者

Sasaki, C.,Miyaguchi, I.,Hagihara, S.,Ishizawa, K.,Endo, J. (登録日: 2024-03-09, 公開日: 2025-03-12, 最終更新日: 2025-12-17)

主引用文献

Hagihara, S.,Ishizawa, K.,Kikuchi, M.,Kawano, Y.,Nishidate, A.,Matsumoto, F.,Hashimoto, N.,Sasaki, C.,Miyaguchi, I.,Okada, O.,Akashi, T.,Nakayama, S.,Ogasawara, Y.,Endo, J.
Discovery of a potent, orally available furopyridine derivative as a novel selective bromodomain and extra-terminal domain (BET)-first bromodomain (BD1) inhibitor.
Bioorg.Med.Chem.Lett., 109:129848-129848, 2024

PubMed Abstract: We explored novel immunosuppressive agents with immune tolerance using a phenotypic drug discovery strategy, focusing on costimulatory molecules in T cells, and obtained triazolothienodiazepine derivatives. Their mechanism of action is to inhibit the bromodomain and extra-terminal domain (BET) family, as we have previously reported. Selective inhibition of the first bromodomain (BD1) of the BET family is expected to exert antitumor and immunosuppressive effects, similar to BET inhibitors. This study identified furopyridine derivatives 7 and 8 with high BD1 inhibitory activity and high selectivity over BD2. Compound 7 was found to be orally bioavailable and exhibited anti-inflammatory activity in a lipopolysaccharide-induced model.

PubMed: 38876176
DOI: 10.1016/j.bmcl.2024.129848

実験手法

X-RAY DIFFRACTION (1.007 Å)