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Issue 8, 2011
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Inhibition of 2-oxoglutarate dependent oxygenases†

Nathan R. Rose,a   Michael A. McDonough,a   Oliver N. F. King,a   Akane Kawamuraa  and  Christopher J. Schofield*a  
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* Corresponding authors

a Department of Chemistry and the Oxford Centre for Integrative Systems Biology, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, UK
E-mail: christopher.schofield@chem.ox.ac.uk
Fax: +44 (0)1865 285002
Tel: +44 (0)1865 275625

Abstract

2-Oxoglutarate (2OG) dependent oxygenases are ubiquitous iron enzymes that couple substrate oxidation to the conversion of 2OG to succinate and carbon dioxide. In humans their roles include collagen biosynthesis, fatty acid metabolism, DNA repair, RNA and chromatin modifications, and hypoxic sensing. Commercial applications of 2OG oxygenase inhibitors began with plant growth retardants, and now extend to a clinically used pharmaceutical compound for cardioprotection. Several 2OG oxygenases are now being targeted for therapeutic intervention for diseases including anaemia, inflammation and cancer. In this critical review, we describe studies on the inhibition of 2OG oxygenases, focusing on small molecules, and discuss the potential of 2OG oxygenases as therapeutic targets (295 references).

Graphical abstract: Inhibition of 2-oxoglutarate dependent oxygenases

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Article information

https://doi.org/10.1039/C0CS00203H
Submitted
03 Dec 2010
First published
10 Mar 2011
Chem. Soc. Rev., 2011,40, 4364-4397
Article type
Critical Review
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Inhibition of 2-oxoglutarate dependent oxygenases

N. R. Rose, M. A. McDonough, O. N. F. King, A. Kawamura and C. J. Schofield, Chem. Soc. Rev., 2011, 40, 4364
DOI: 10.1039/C0CS00203H

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