5FP4

Crystal structure of human KDM4D in complex with 3-(4- phenylbutanamido)pyridine-4-carboxylic acid

Summary for 5FP4

• Entry DOI: 10.2210/pdb5fp4/pdb
• Related: 5FP3 5FP7 5FP8 5FP9 5FPA 5FPB
• Descriptor: LYSINE-SPECIFIC DEMETHYLASE 4D, ZINC ION, FE (II) ION, ... (7 entities in total)
• Functional Keywords: transcription, inhibitor, lysine specific histone demethylase, jmjd2d, kdm4d, jumonji
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus : Q6B0I6
• Total number of polymer chains: 1
• Total formula weight: 39888.92

Authors

Chung, C. (deposition date: 2015-11-27, release date: 2016-01-27, Last modification date: 2024-05-08)

Primary citation

Westaway, S.M.,Preston, A.G.S.,Barker, M.D.,Brown, F.,Brown, J.A.,Campbell, M.,Chung, C.,Diallo, H.,Douault, C.,Drewes, G.,Eagle, R.,Gordon, L.,Haslam, C.,Hayhow, T.G.,Humphreys, P.G.,Joberty, G.,Katso, R.,Kruidenier, L.,Leveridge, M.,Liddle, J.,Mosley, J.,Muelbaier, M.,Randle, R.,Rioja, I.,Rueger, A.,Seal, G.A.,Sheppard, R.J.,Singh, O.,Taylor, J.,Thomas, P.,Thomson, D.,Wilson, D.M.,Lee, K.,Prinjha, R.K.
Cell Penetrant Inhibitors of the Kdm4 and Kdm5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-Pyridine Carboxylate Derivatives.
J.Med.Chem., 59:1357-, 2016

PubMed Abstract: Optimization of KDM6B (JMJD3) HTS hit 12 led to the identification of 3-((furan-2-ylmethyl)amino)pyridine-4-carboxylic acid 34 and 3-(((3-methylthiophen-2-yl)methyl)amino)pyridine-4-carboxylic acid 39 that are inhibitors of the KDM4 (JMJD2) family of histone lysine demethylases. Compounds 34 and 39 possess activity, IC50 ≤ 100 nM, in KDM4 family biochemical (RFMS) assays with ≥ 50-fold selectivity against KDM6B and activity in a mechanistic KDM4C cell imaging assay (IC50 = 6-8 μM). Compounds 34 and 39 are also potent inhibitors of KDM5C (JARID1C) (RFMS IC50 = 100-125 nM).

PubMed: 26771107
DOI: 10.1021/ACS.JMEDCHEM.5B01537

Experimental method

X-RAY DIFFRACTION (2 Å)