6CG1

Crystal Structure of KDM4A with Compound 14

Summary for 6CG1

• Entry DOI: 10.2210/pdb6cg1/pdb
• Descriptor: Lysine-specific demethylase 4A, NICKEL (II) ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: kdm4a, small molecule inhibitor, demethylase, oxidoreductase, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : O75164
• Total number of polymer chains: 4
• Total formula weight: 164527.12

Authors

Hosfield, D.J.,Nie, Z. (deposition date: 2018-02-19, release date: 2018-04-18, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.16 Å)