6CG2

Crystal Structure of KDM4A with Compound 8

6CG2 の概要

• エントリーDOI: 10.2210/pdb6cg2/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: kdm4a, small molecule inhibitor, demethylase, oxidoreductase, 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: 164667.24

構造登録者

Hosfield, D.J.,Nie, Z. (登録日: 2018-02-19, 公開日: 2018-04-18, 最終更新日: 2023-10-04)

主引用文献

Nie, Z.,Shi, L.,Lai, C.,O'Connell, S.M.,Xu, J.,Stansfield, R.K.,Hosfield, D.J.,Veal, J.M.,Stafford, J.A.
Structure-based design and discovery of potent and selective KDM5 inhibitors.
Bioorg. Med. Chem. Lett., 28:1490-1494, 2018

PubMed Abstract: Histone lysine demethylases (KDMs) play a key role in epigenetic regulation and KDM5A and KDM5B have been identified as potential anti-cancer drug targets. Using structural information from known KDM4 and KDM5 inhibitors, a potent series of pyrazolylpyridines was designed. Structure-activity relationship (SAR) exploration resulted in the identification of compound 33, an orally available, potent inhibitor of KDM5A/5B with promising selectivity. Potent cellular inhibition as measured by levels of tri-methylated H3K4 was demonstrated with compound 33 in the breast cancer cell line ZR-75-1.

PubMed: 29627262
DOI: 10.1016/j.bmcl.2018.03.083

実験手法

X-RAY DIFFRACTION (2.34 Å)