5VMP

Crystal Structure of Human KDM4 with Small Molecule Inhibitor QC5714

5VMP の概要

• エントリーDOI: 10.2210/pdb5vmp/pdb
• 分子名称: Lysine-specific demethylase 4A, NICKEL (II) ION, ZINC ION, ... (5 entities in total)
• 機能のキーワード: kdm4, inhibitor-complex, demethylase, epigenetics, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : O75164
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 173648.94

構造登録者

Hosfield, D.J. (登録日: 2017-04-28, 公開日: 2017-09-27, 最終更新日: 2023-10-04)

主引用文献

Chen, Y.K.,Bonaldi, T.,Cuomo, A.,Del Rosario, J.R.,Hosfield, D.J.,Kanouni, T.,Kao, S.C.,Lai, C.,Lobo, N.A.,Matuszkiewicz, J.,McGeehan, A.,O'Connell, S.M.,Shi, L.,Stafford, J.A.,Stansfield, R.K.,Veal, J.M.,Weiss, M.S.,Yuen, N.Y.,Wallace, M.B.
Design of KDM4 Inhibitors with Antiproliferative Effects in Cancer Models.
ACS Med Chem Lett, 8:869-874, 2017

PubMed Abstract: Histone lysine demethylases (KDMs) play a vital role in the regulation of chromatin-related processes. Herein, we describe our discovery of a series of potent KDM4 inhibitors that are both cell permeable and antiproliferative in cancer models. The modulation of histone H3K9me3 and H3K36me3 upon compound treatment was verified by homogeneous time-resolved fluorescence assay and by mass spectroscopy detection. Optimization of the series using structure-based drug design led to compound (QC6352), a potent KDM4 family inhibitor that is efficacious in breast and colon cancer PDX models.

PubMed: 28835804
DOI: 10.1021/acsmedchemlett.7b00220

実験手法

X-RAY DIFFRACTION (2.48 Å)