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Published on: August 2, 2018
Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases
Rasheduzzaman Chowdhury1, José Ignacio Candela-Lena, Mun Chiang Chan
1Department of Chemistry, Chemistry Research Laboratory, University of Oxford , Mansfield Road, Oxford, OX1 3TA, United Kingdom.
None:
The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in animals. The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, we describe biochemical, crystallographic, cellular profiling, and animal studies on PHD inhibitors including selectivity studies using a representative set of human 2OG oxygenases. We identify suitable probe compounds for use in studies on the functional effects of PHD inhibition in cells and in animals.
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