Daprodustat
Daprodustat is an inhibitor of hypoxia-inducible factor prolyl hydroxylase 1 (HIF-PH1), HIF-PH2, and HIF-PH3 (IC50s = 3.5, 22.2, 5.5 nM, respectively).{62576} It is selective for HIF-PH1, -2, and -3 over factor-inhibiting HIF (FIH) and collagen prolyl hydroxylase (CP4H; IC50s = 9,800 and >200,000 nM, respectively). Daprodustat (25 and 50 µM) induces accumulation of HIF-1? and HIF-2? in Hep3B cells. In vivo, daprodustat (60 mg/kg) increases plasma levels of erythropoietin (EPO) in mice. It increases the number of reticulocytes and levels of hemoglobin in mice when administered at doses of 3, 10, and 30 mg/kg.
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