5KR7

KDM4C bound to pyrazolo-pyrimidine scaffold

5KR7 の概要

• エントリーDOI: 10.2210/pdb5kr7/pdb
• 分子名称: Lysine-specific demethylase 4C, FE (II) ION, ZINC ION, ... (6 entities in total)
• 機能のキーワード: inhibitor, histone, lysine demethylase, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : Q9H3R0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 85420.44

構造登録者

Bellon, S.F.,Poy, F.,Setser, J.W. (登録日: 2016-07-07, 公開日: 2016-08-17, 最終更新日: 2023-10-04)

主引用文献

Gehling, V.S.,Bellon, S.F.,Harmange, J.C.,LeBlanc, Y.,Poy, F.,Odate, S.,Buker, S.,Lan, F.,Arora, S.,Williamson, K.E.,Sandy, P.,Cummings, R.T.,Bailey, C.M.,Bergeron, L.,Mao, W.,Gustafson, A.,Liu, Y.,VanderPorten, E.,Audia, J.E.,Trojer, P.,Albrecht, B.K.
Identification of potent, selective KDM5 inhibitors.
Bioorg.Med.Chem.Lett., 26:4350-4354, 2016

PubMed Abstract: This communication describes the identification and optimization of a series of pan-KDM5 inhibitors derived from compound 1, a hit initially identified against KDM4C. Compound 1 was optimized to afford compound 20, a 10nM inhibitor of KDM5A. Compound 20 is highly selective for the KDM5 enzymes versus other histone lysine demethylases and demonstrates activity in a cellular assay measuring the increase in global histone 3 lysine 4 tri-methylation (H3K4me3). In addition compound 20 has good ADME properties, excellent mouse PK, and is a suitable starting point for further optimization.

PubMed: 27476424
DOI: 10.1016/j.bmcl.2016.07.026

実験手法

X-RAY DIFFRACTION (1.9 Å)