FG-2216

SKU: orb1225617

Description

FG-2216 (YM-311, IOX3) is a selective small molecule inhibitor of HIF prolyl hydroxylase with IC50 of 3.9 nM (PDH2), decreases protein expression of DNA/RNA demethylase FTO (in C2C12 cells) and reduces maximal respiration rate in vitro; up-regulates HIF-1α and increases erythropoietin expression in mice, also significantly reduces bone mineral density and content and alter adipose tissue distribution in mice; FG-2216 is orally bioavailable and induced significant and reversible Epo induction in vivo.(In Vitro):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.(In Vivo):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.

Key Properties

• CAS Number: 223387-75-5
• MW: 280.7
• Purity: >98% (HPLC)
• Formula: C₁₂H₉ClN₂O₄
• SMILES: OC1=C(C(NCC(O)=O)=O)N=C(Cl)C2=CC=CC=C21
• Target: HIF/HIF Prolyl-hydroxylase
• Solubility: DMSO: ≥ 31 mg/mL

Bioactivity

• In Vivo:
  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.
• In Vitro:
  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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

YM-311 | IOX3

Quick Database Links

Gene Symbol

HIF/HIF Prolyl-hydroxylase