6EIV

DYRK1A in complex with JWD-065

6EIV の概要

• エントリーDOI: 10.2210/pdb6eiv/pdb
• 分子名称: Dual specificity tyrosine-phosphorylation-regulated kinase 1A, ~{N}-[3-[[4-azanyl-2-[[4-(4-methylpiperazin-1-yl)phenyl]amino]-1,3-thiazol-5-yl]carbonyl]phenyl]propanamide (3 entities in total)
• 機能のキーワード: dual specificity tyrosine-phosphorylation-regulated kinase 1a, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 172474.30

構造登録者

Rothweiler, U. (登録日: 2017-09-19, 公開日: 2018-08-29, 最終更新日: 2024-10-16)

主引用文献

Czarna, A.,Wang, J.,Zelencova, D.,Liu, Y.,Deng, X.,Choi, H.G.,Zhang, T.,Zhou, W.,Chang, J.W.,Kildalsen, H.,Seternes, O.M.,Gray, N.S.,Engh, R.A.,Rothweiler, U.
Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors.
J. Med. Chem., 61:7560-7572, 2018

PubMed Abstract: DYRK1A is one of five members of the dual-specificity tyrosine (Y) phosphorylation-regulated kinase (DYRK) family. The DYRK1A gene is located in the Down syndrome critical region and regulates cellular processes related to proliferation and differentiation of neuronal progenitor cells during early development. This has focused research on its role in neuronal degenerative diseases, including Alzheimer's and Down syndrome. Recent studies have also shown a possible role of DYRK1A in diabetes. Here we report a variety of scaffolds not generally known for DYRK1A inhibition, demonstrating their effects in in vitro assays and also in cell cultures. These inhibitors effectively block the tau phosphorylation that is a hallmark of Alzheimer's disease. The crystal structures of these inhibitors support the design of optimized and novel therapeutics.

PubMed: 30095246
DOI: 10.1021/acs.jmedchem.7b01847

実験手法

X-RAY DIFFRACTION (2.68 Å)