FG-2216 (IOX3) is a potent and orally active inhibitor of HIF prolyl hydroxylase-2 (PHD2), with an IC50 of 3.9 nM. FG-2216 induces robust erythropoietin and modest fetal hemoglobin in vivo.
IC50&Target
IC50: 3.9 nM (PHD2)
体外研究
FG-2216 (50-100 μM; 24 h) stimulates erythropoietin (Epo) secretion by PHD2 inhibition in Hep3B cells.
FG-2216 (3-100 μM; 24 h) stabilizes HIF-1α and HIF-2α in Hep3B cells.
体内研究
FG-2216 (40-60 mg/kg; p.o. twice a week for 150 d) induces erythropoiesis and a small elevation of hemoglobin (HbF) expression, and is well tolerated in rhesus macaques.
FG-2216 (50 mg/kg; p.o. once daily for 4 or 12 d) increases hematocrit, red blood cell counts, and hemoglobin levels in mice.
FG-2216 (40-60 mg/kg; a single p.o) reversibly induces endogenous Epo in rhesus macaques.
Animal Model:
Male rhesus macaques (3-6 years; 4-7 kg) mice are treated with large-volume phlebotomy with iron supplementation
Dosage:
40, 60 mg/kg
Administration:
P.o. (40 mg/kg) twice a week for 6-8 weeks
P.o. (60 mg/kg) twice a week for 6-8 weeks
P.o. (60 mg/kg) twice a week for 6-8 weeks
Result:
Exhibited reticulocytosis within 1-2 weeks of dosing.
Increased total hemoglobin levels at the end of the study duration.
分子式
C12H9ClN2O4
分子量
280.66
CAS号
223387-75-5
运输条件
Room temperature in continental US; may vary elsewhere.