Hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) enzymes act as central gatekeepers of post-transcriptional and transcriptional adaptation to hypoxia, oxidative stress, and excitotoxicity. FG-2216 is an orally active PHD2 inhibitor (IC50 = 3.9 μM) that stabilizes HIF-α. It has been shown to reversibly stimulate erythropoietin secretion at 100 μM in vitro and to increase hematocrit, red blood cell count, and hemoglobin levels at 50 mg/kg in mice.
