Inhibition of 2-oxoglutarate dependent oxygenases.

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).

• Authors: Nathan R Rose, Michael A McDonough, Oliver N F King, Akane Kawamura, Christopher J Schofield
• Journal: Chemical Society reviews (Chem Soc Rev) Vol. 40 Issue 8 Pg. 4364-97 (Aug 2011) ISSN: 1460-4744 [Electronic] England
• PMID: 21390379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: This journal is © The Royal Society of Chemistry 2011

Chemical References

• Enzyme Inhibitors
• Ethylenes
• Gibberellins
• Ketoglutaric Acids
• Metals
• Collagen
• ethylene
• Succinic Acid
• Mixed Function Oxygenases
• gamma-Butyrobetaine Dioxygenase
• Procollagen-Proline Dioxygenase

Topics

• Collagen (biosynthesis)
• Enzyme Inhibitors (chemistry, pharmacology)
• Ethylenes (biosynthesis)
• Gibberellins (metabolism)
• Humans
• Ketoglutaric Acids (metabolism)
• Metals (pharmacology)
• Mixed Function Oxygenases (antagonists & inhibitors, chemistry, metabolism)
• Procollagen-Proline Dioxygenase (antagonists & inhibitors, metabolism)
• Succinic Acid (metabolism)
• gamma-Butyrobetaine Dioxygenase (antagonists & inhibitors)