HIF-PHD-IN-1

HIF-PHD-IN-1 is a pharmacological compound that acts as an orally active inhibitor of the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD), displaying an IC50 of 54 nM for hHIF-PHD2. Its potential as a therapeutic agent for renal anemia is highly promising.

HIF-PHD-IN-1 (compound 19) (0.5-2 mg/kg; p. o. once daily for 4 weeks) improves hemoglobin levels in anemic rats[1]. HIF-PHD-IN-1 (10 mg/kg; single p.o.) increases serum erythropoietin (EPO) concentration at 8 h after administration in SD rats[1]. HIF-PHD-IN-1 (1 mg/kg; p.o.) shows good bioavailability (F=77%) in male SD rats[1]. Animal Model: Male SD Rats excising ?ve-sixths of their kidneys[1]Dosage: 0.5, 1, 2 mg/kg Administration: P.o. once daily for 4 weeks Result: Improved blood hemoglobin levels starting at weeks 2 and 1 in the groups receiving 1 and 2 (mg/kg)/day, respectively. Animal Model: Male SD Rats[1]Dosage: 1 mg/kg (Pharmacokinetic Analysis) Administration: Single p.o. or i.v. Result: C max =1839 ng/mL (p.o.); C max =12357ng/mL (i.v.); F=77%.

1. Goi T, et, al. Pyrazolo[4,3- d]pyrimidine Derivatives as a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Domain Inhibitor for the Treatment of Anemia. ACS Med Chem Lett. 2020 Jun 4; 11(7): 1416-1420.