5KR7

KDM4C bound to pyrazolo-pyrimidine scaffold

Summary for 5KR7

• Entry DOI: 10.2210/pdb5kr7/pdb
• Descriptor: Lysine-specific demethylase 4C, FE (II) ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: inhibitor, histone, lysine demethylase, oxidoreductase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q9H3R0
• Total number of polymer chains: 2
• Total formula weight: 85420.44

Authors

Bellon, S.F.,Poy, F.,Setser, J.W. (deposition date: 2016-07-07, release date: 2016-08-17, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)