6TE1

Structure of the KDM1A/CoREST complex with the inhibitor 2-[3-{4-chloro-3-[(4-chlorophenyl)ethynyl]phenyl}-1-(3-morpholin-4-ylpropyl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-2-oxoethanol

6TE1 の概要

• エントリーDOI: 10.2210/pdb6te1/pdb
• 分子名称: Lysine-specific histone demethylase 1A, REST corepressor 1, 5-[4-cyclobutyl-1-[2-(4-piperidin-4-yloxyphenoxy)ethyl]imidazol-2-yl]-4-methyl-thieno[3,2-b]pyrrole, ... (6 entities in total)
• 機能のキーワード: histone demethylase, inhibitor, complex, oxidoreductase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 148312.70

構造登録者

Pasqualato, S.,Cecatiello, V. (登録日: 2019-11-11, 公開日: 2020-06-03, 最終更新日: 2024-01-24)

主引用文献

Romussi, A.,Cappa, A.,Vianello, P.,Brambillasca, S.,Cera, M.R.,Dal Zuffo, R.,Faga, G.,Fattori, R.,Moretti, L.,Trifiro, P.,Villa, M.,Vultaggio, S.,Cecatiello, V.,Pasqualato, S.,Dondio, G.,So, C.W.E.,Minucci, S.,Sartori, L.,Varasi, M.,Mercurio, C.
Discovery of Reversible Inhibitors of KDM1A Efficacious in Acute Myeloid Leukemia Models.
Acs Med.Chem.Lett., 11:754-759, 2020

PubMed Abstract: Lysine-specific demethylase 1 (LSD1 or KDM1A) is a FAD-dependent enzyme that acts as a transcription corepressor or coactivator by regulating the methylation status of histone H3 lysines K4 and K9, respectively. KDM1A represents an attractive target for cancer therapy. While, in the past, the main medicinal chemistry strategy toward KDM1A inhibition was based on the optimization of ligands that irreversibly bind the FAD cofactor within the enzyme catalytic site, we and others have also identified reversible inhibitors. Herein we reported the discovery of 5-imidazolylthieno[3,2-]pyrroles, a new series of KDM1A inhibitors endowed with picomolar inhibitory potency, active in cells and efficacious after oral administration in murine leukemia models.

PubMed: 32435381
DOI: 10.1021/acsmedchemlett.9b00604

実験手法

X-RAY DIFFRACTION (3.11 Å)