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Biological Activity:

IOX4 is a potent and selective PHD2 inhibitor with IC50 ~1.6 nM. It inhibits PHD2 via binding to the 2OG , displays >1,000-fold selectivity for PHD2 over other 2OG-dependent dioxygenases, including JMJD isoforms, FBXL11, JARID1C, BBOX1, FIH, and FTO. IOX4 is active in vivo, inhibiting prolyl hydroxylation and increasing HIF-1α levels in cells (IC50 ~5.6-11.7 µM) and inducing HIF-1α and HIF-2α expression in mice. The induction of HIF expression in mice occurs in the brain as well as in the liver, kidney, and heart, indicating that IOX4 penetrates the blood-brain barrier. IOX4 could be a useful tool compound for studies aimed at validating the upregulation of HIF for treatment of cerebral diseases including stroke.

How to Use:

In vitro: IOX4 was used at 10-50 µM final concentration in vitro and in cellular assays.
In vivo: IOX4 was dosed to mice by IP injection at 17.5-70 mg/kg.