Inhibition of Histone Demethylases by 4-Carboxy-2,2-Bipyridyl Compounds

DOI: 10.1002/cmdc.201100026
PMID: 21412984

Authors: Kai-hsuan Chang (University of Oxford) , Oliver King (University of Oxford) , Antony Tumber (University of Oxford) , Esther Woon (University of Oxford) , Tom Heightman (University of Oxford) , Michael Mcdonough (University of Oxford) , Christopher Schofield (University of Oxford) , Nathan Rose (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chemmedchem , VOL 6 (5) , PAGES 759 - 764

State: Published (Approved)
Published: March 2011

Abstract: 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 110 nM, representing a 66-fold improvement over the lead compound. These bipyridyl derivatives bind in the 2-oxoglutarate binding site.

Journal Keywords: Binding; Computer; Crystallography; X-Ray; Enzyme; Humans; Jumonji; Ketoglutaric; Protein; Tertiary; Structure-Activity Relationship

Subject Areas: Chemistry


Instruments: I02-Macromolecular Crystallography