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-PHD2 (human):54 nM (IC50)

HIF-PHD-IN-1 (compound 19), administered orally at doses of 0.5-2 mg/kg once daily for four weeks, enhances hemoglobin levels in anemic rats, indicating potential effectiveness in treating anemia. A single oral dose of 10 mg/kg significantly increases serum erythropoietin (EPO) levels 8 hours post-administration in Sprague-Dawley (SD) rats, suggesting a stimulatory effect on erythropoiesis. At 1 mg/kg, HIF-PHD-IN-1 shows good bioavailability (F=77%) in male SD rats, indicating efficient absorption. This study used male SD rats with five-sixths nephrectomy to simulate anemia. The results show improved hemoglobin levels starting at weeks 2 and 1 for the 1 and 2 mg/kg/day groups, respectively. Pharmacokinetic analysis at 1 mg/kg, administered orally or intravenously, showed Cmax values of 1839 ng/mL (oral) and 12357 ng/mL (intravenous), with a bioavailability of 77%.