HIF-prolyl hydroxylase-2 (PHD2) inhibitor. Blocks glutamate induced ROS production in HT-22 cells, independent of MnSOD. Exhibits neuroprotective effects and enhances functional recovery in rodent intracerebral hemorrhage models, via inhibition of ATF4 dependent genes. Brain penetrant. Also antioxidant.
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Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models.
Karuppagounder et al.
Inhibition of HIF-prolyl-4-hydroxylases prevents mitochondrial impairment and cell death in a model of neuronal oxytosis.
Neitemeier et al.
Cell Death Dis., 2016;7:e2214