5W6E

PDE1b complexed with compound 3S

5W6E の概要

• エントリーDOI: 10.2210/pdb5w6e/pdb
• 分子名称: Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: phosphodiesterase, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 42552.04

構造登録者

Vajdos, F.F. (登録日: 2017-06-16, 公開日: 2018-05-30, 最終更新日: 2024-03-13)

主引用文献

Humphrey, J.M.,Movsesian, M.,Am Ende, C.W.,Becker, S.L.,Chappie, T.A.,Jenkinson, S.,Liras, J.L.,Liras, S.,Orozco, C.,Pandit, J.,Vajdos, F.F.,Vandeput, F.,Yang, E.,Menniti, F.S.
Discovery of Potent and Selective Periphery-Restricted Quinazoline Inhibitors of the Cyclic Nucleotide Phosphodiesterase PDE1.
J. Med. Chem., 61:4635-4640, 2018

PubMed Abstract: We disclose the discovery and X-ray cocrystal data of potent, selective quinazoline inhibitors of PDE1. Inhibitor ( S)-3 readily attains free plasma concentrations above PDE1 IC values and has restricted brain access. The racemic compound 3 inhibits >75% of PDE hydrolytic activity in soluble samples of human myocardium, consistent with heightened PDE1 activity in this tissue. These compounds represent promising new tools to probe the value of PDE1 inhibition in the treatment of cardiovascular disease.

PubMed: 29718668
DOI: 10.1021/acs.jmedchem.8b00374

実験手法

X-RAY DIFFRACTION (1.9 Å)