Inhibition of histone demethylases by 4-carboxy-2,2'-bipyridyl compounds.

Journal article

Exploiting epigenetics: 2-Oxoglutarate (2OG)-dependent histone lysine demethylases, such as JMJD2E, are potential therapeutic targets in a range of diseases. Through structure-activity relationship studies and analyses, we identified a potent 4-carboxy-2,2'-bipyridyl compound, which inhibits JMJD2E with an IC50 value of 110nM, representing a 66-fold improvement over the lead compound. These bipyridyl derivatives bind in the 2-oxoglutarate binding site. © 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

Authors: Chang, K; King, O; Tumber, A; Woon, E; Heightman, T

• Publication status: Published
• Journal: ChemMedChem
• Volume: 6
• Issue: 5
• Pages: 759-764
• Publication date: 2011-05-01
• DOI: 10.1002/cmdc.201100026
• EISSN: 1860-7187
• ISSN: 1860-7179
• Language: English
• Keywords: 2,2'-Dipyridyl; Computer Simulation; Crystallography, X-Ray; Ketoglutaric Acids; Humans; Enzyme Inhibitors; Binding Sites; Protein Structure, Tertiary; Structure-Activity Relationship; Jumonji Domain-Containing Histone Demethylases