5VGI

Crystal Structure of KDM4 with the Small Molecule Inhibitor QC6352

Summary for 5VGI

• Entry DOI: 10.2210/pdb5vgi/pdb
• Related: 5VGK
• Descriptor: Lysine-specific demethylase 4A, NICKEL (II) ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: kdm4, protein-inhibitor complex, demethylase, epigenetics, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : O75164
• Total number of polymer chains: 4
• Total formula weight: 174598.13

Authors

Hosfield, D.J. (deposition date: 2017-04-11, release date: 2017-09-27, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.07 Å)