tert-butyl 6-(5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinate

개요IOX4 is a potent inhibitor of hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2; IC50 = 1.6 nM). It 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 values range from 5.6 to 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.

용도IOX4 is a triazole based potent and selective inhibitor of hypoxia-inducible factor (HIF) prolyl-hydroxylase. It induces HIFα in cells of mouse brain. It is useful for studies that aim to validate the upregulation of HIF for treatment of cerebral diseases such as stroke.