Inhibition of 2-oxoglutarate dependent oxygenases

• Published in: Chemical Society reviews Vol. 40; no. 8; pp. 4364 - 4397
• Main Authors: Rose, Nathan R, McDonough, Michael A, King, Oliver N F, Kawamura, Akane, Schofield, Christopher J
• Format: Journal Article
• Language: English
• Published: England 01.01.2011
• Subjects: Collagen - biosynthesis; Diseases; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzymes; Ethylenes - biosynthesis; Fatty acids; Focusing; gamma-Butyrobetaine Dioxygenase - antagonists & inhibitors; Gibberellins - metabolism; Humans; Inhibition; Inhibitors; Iron and steel plants; Ketoglutaric Acids - metabolism; Metals - pharmacology; Mixed Function Oxygenases - antagonists & inhibitors; Mixed Function Oxygenases - chemistry; Mixed Function Oxygenases - metabolism; Procollagen-Proline Dioxygenase - antagonists & inhibitors; Procollagen-Proline Dioxygenase - metabolism; Ribonucleic acids; Succinic Acid - metabolism
• ISSN: 0306-0012; 1460-4744
• DOI: 10.1039/c0cs00203h

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).