3WS8

Crystal structure of PDE10A in complex with a benzimidazole inhibitor

3WS8 の概要

• エントリーDOI: 10.2210/pdb3ws8/pdb
• 関連するPDBエントリー: 3WS9
• 分子名称: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: phosphodiesterase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9Y233
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80127.18

構造登録者

Amano, Y.,Honbou, K. (登録日: 2014-03-04, 公開日: 2014-06-04, 最終更新日: 2023-11-08)

主引用文献

Chino, A.,Masuda, N.,Amano, Y.,Honbou, K.,Mihara, T.,Yamazaki, M.,Tomishima, M.
Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability.
Bioorg.Med.Chem., 22:3515-3526, 2014

PubMed Abstract: In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition.

PubMed: 24837154
DOI: 10.1016/j.bmc.2014.04.023

実験手法

X-RAY DIFFRACTION (2.6 Å)