TP-0463518 is a pan hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor.1 It inhibits human HIF-PH1 (Ki = 5.3 nM), as well as human HIF-PH2 and HIF-PH3 (IC50s = 18 and 63 nM, respectively). TP-0463518 (5 mg/kg) increases serum levels of erythropoietin (EPO) in mice. It also increases serum EPO levels in a 5/6 nephrectomy-induced rat model of chronic kidney disease when administered at a dose of 10 mg/kg.
1.Kato, S., Takayama, N., Takano, H., et al.TP0463518, a novel inhibitor for hypoxia-inducible factor prolyl hydroxylases, increases erythropoietin in rodents and monkeys with a good pharmacokinetics-pharmacodynamics correlationEur. J. Pharmacol.838138-144(2018)