FG-2216 is a potent HIF-prolyl hydroxylase inhibitor. IC50 = 3.9 μM for PDH2 enzyme.
HIFs (hypoxia inducible factors) are transcription factor that activated by low oxygen availability. It leads to cellular, tissue and organismal adaptive response to hypoxia. Increased hemoglobin
levels are associated with intrauterine hypoxia. In cooperation with other transcriptional coactivators, HIF induces transcription of genes that ameliorate the effects of hypoxia, including erythropoietin and its receptor.
In rhesus macaques, FG-2216 reversibly activates endogenous erythropoietin (82- to 309-fold at 60 mg/kg), and as early as 4 hours after oral administration of FG-2216, circulating plasma Epo levels increases. [1]
Chronic administration of FG-2216 is well tolerated and induces erythropoiesis in rhesus macaques. It also induced a small elevation of hemoglobin expression in vivo. FG-2216–treated animals exerts rise in the percentage of hemoglobin-containing reticulocytes (% F+ retics) 1 to 2 weeks after chronic dosing began. [1]
Reference:
1. Hsieh MM, Linde NS, Wynter A et al. HIF prolyl hydroxylase inhibition
results in endogenous erythropoietin induction, erythrocytosis, and modest fetal
hemoglobin expression in rhesus macaques. Blood. 2007 Sep 15;110(6):2140-7.