5FP3

Cell penetrant inhibitors of the JMJD2 (KDM4) and JARID1 (KDM5) families of histone lysine demethylases

Summary for 5FP3

• Entry DOI: 10.2210/pdb5fp3/pdb
• Related: 5FP4 5FP7 5FP8 5FP9 5FPA 5FPB
• Descriptor: HUMAN LYSINE-SPECIFIC DEMETHYLASE 6B, JMJD3, 3-(4-phenylbutanoylamino)pyridine-4-carboxylic acid, ZINC ION, ... (7 entities in total)
• Functional Keywords: oxidoreductase, inhibitor, jmjd3, kdm6b, jumonji
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 117667.78

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 (2.05 Å)