6MSA

Novel, potent, selective and brain penetrant phosphodiesterase 10A inhibitors

6MSA の概要

• エントリーDOI: 10.2210/pdb6msa/pdb
• 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
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77149.93

構造登録者

Jakob, C.G. (登録日: 2018-10-16, 公開日: 2019-01-09, 最終更新日: 2024-03-13)

主引用文献

Geneste, H.,Drescher, K.,Jakob, C.,Laplanche, L.,Ochse, M.,Torrent, M.
Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors.
Bioorg. Med. Chem. Lett., 29:406-412, 2019

PubMed Abstract: Herein we report the discovery of a novel series of phosphodiesterase 10A inhibitors. Optimization of a HTS hit (17) resulted in potent, selective, and brain penetrant 23 and 26; both exhibited much lower clearance in vivo and decreased volume of distribution (rat PK) and have thus the potential to inhibit the PDE10A target in vivo at a lower efficacious dose than the reference compound WEB-3.

PubMed: 30587449
DOI: 10.1016/j.bmcl.2018.12.029

実験手法

X-RAY DIFFRACTION (2.06 Å)