4HEU

Crystal Structure of PDE10A with a biaryl ether inhibitor ((1-(3-(4-((1H-benzo[d]imidazol-2-yl)amino)phenoxy)pyridin-2-yl)piperidin-4-yl)methanol)

4HEU の概要

• エントリーDOI: 10.2210/pdb4heu/pdb
• 関連するPDBエントリー: 4DDL 4HF4
• 分子名称: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, ZINC ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: pde10a, inhibitors, phosphodiesterase 10a, biaryl ethers, 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: 75960.25

構造登録者

Chmait, S.,Jordan, S. (登録日: 2012-10-04, 公開日: 2012-12-12, 最終更新日: 2024-11-27)

主引用文献

Rzasa, R.M.,Hu, E.,Rumfelt, S.,Chen, N.,Andrews, K.L.,Chmait, S.,Falsey, J.R.,Zhong, W.,Jones, A.D.,Porter, A.,Louie, S.W.,Zhao, X.,Treanor, J.J.,Allen, J.R.
Discovery of selective biaryl ethers as PDE10A inhibitors: Improvement in potency and mitigation of Pgp-mediated efflux.
Bioorg.Med.Chem.Lett., 22:7371-7375, 2012

PubMed Abstract: We report the discovery of a novel series of biaryl ethers as potent and selective PDE10A inhibitors. Structure-activity studies improved the potency and decreased Pgp-mediated efflux found in the initial compound 4. X-ray crystallographic studies revealed two novel binding modes to the catalytic site of the PDE10A enzyme.

PubMed: 23149228
DOI: 10.1016/j.bmcl.2012.10.078

実験手法

X-RAY DIFFRACTION (2 Å)