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 N, F. King (University of Oxford) , Antony Tumber (University of Oxford) , Esther C. Y. Woon (University of Oxford) , Tom D. Heightman (University of Oxford) , Michael A. Mcdonough (University of Oxford) , Christopher J. Schofield (University of Oxford) , Nathan R. 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: bipyridyl derivatives; epigenetics; histone; demethylases; inhibitors; 2-oxoglutarate

Diamond Keywords: Epigenetics

Subject Areas: Chemistry, Biology and Bio-materials, Medicine


Instruments: I02-Macromolecular Crystallography

Added On: 06/04/2011 10:38

Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Structural biology Organic Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)