Dual-action inhibitors of HIF prolyl hydroxylases that induce binding of a second iron ion

…, MC Chan, A Thalhammer, M Demetriades…

Index: Yeoh, Kar Kheng; Chan, Mun Chiang; Thalhammer, Armin; Demetriades, Marina; Chowdhury, Rasheduzzaman; Tian, Ya-Min; Stolze, Ineke; McNeill, Luke A.; Lee, Myung Kyu; Woon, Esther C. Y.; MacKeen, Mukram M.; Kawamura, Akane; Ratcliffe, Peter J.; Mecinovic, Jasmin; Schofield, Christopher J. Organic and Biomolecular Chemistry, 2013 , vol. 11, # 5 p. 732 - 745

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Citation Number: 6

Abstract

Inhibition of the hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD or EGLN enzymes) is of interest for the treatment of anemia and ischemia-related diseases. Most PHD inhibitors work by binding to the single ferrous ion and competing with 2-oxoglutarate (2OG) co- substrate for binding at the PHD active site. Non-specific iron chelators also inhibit the PHDs, both in vitro and in cells. We report the identification of dual action PHD inhibitors, ...