A pan HIF-PH inhibitor
Enarodustat is a pan hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor (Kis = 16, 61, and 101 nM for HIF-PH1, -2, and -3, respectively).1 It increases erythropoietin (EPO) levels in Hep3B cells (EC50 = 4.7 ?M). Enarodustat (3 mg/kg) increases plasma EPO levels in control rats, as well as plasma EPO and hemoglobin levels in 5/6-nephrectomized rats. It also decreases renal fatty acid and amino acid metabolism and increases renal glucose metabolism in streptozotocin-induced rat and alloxan-induced mouse models of diabetic nephropathy.2
1.Fukui, K., Shinozaki, Y., Kobayashi, H., et al.JTZ-951 (enarodustat), a hypoxia-inducibe factor prolyl hydroxylase inhibitor, stabilizes HIF-α protein and induces erythropoiesis without effects on the function of vascular endothelial growth factorEur. J. Pharmacol.859172532(2019) 2.Hasegawa, S., Tanaka, T., Saito, T., et al.The oral hypoxia-inducible factor prolyl hydroxylase inhibitor enarodustat counteracts alterations in renal energy metabolism in the early stages of diabetic kidney diseaseKidney Int.97(5)934-950(2020)
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