1 research outputs found
Selective Small Molecule Probes for the Hypoxia Inducible Factor (HIF) Prolyl Hydroxylases
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