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Purity: ≥98%
FG-2216 (YM311; IOX3; YM311) is a novel, potent, and orally bioactive inhibitor of hypoxia-inducible factor-1α (HIF) prolyl 4-hydroxylase (PHD) with the potential to treat anemia. It inhibits HIF-PHD with an IC50 of 3.9 μM.
| ln Vitro |
In Hep3B cells, FG-2216 (50-100 μM; 24 h) increases erythropoietin (Epo) secretion through PHD2 inhibition[1]. In Hep3B cells, FG-2216 (3-100 μM; 24 h) stabilizes HIF-1α and HIF-2α[1].
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| ln Vivo |
Rhesus macaques respond well to FG-2216 (40–60 mg/kg; po twice weekly for 150 days), which causes erythropoiesis and a little increase in hemoglobin (HbF) expression[2]. In mice, FG-2216 (50 mg/ kg; po once daily for 4 or 12 d) raises hemoglobin levels, red blood cell counts, and hematocrit[1]. In rhesus macaques, FG-2216 (40–60 mg/kg; one po) reversibly produces endogenous Epo [2].
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| Animal Protocol |
Animal/Disease Models: Male rhesus macaques (3-6 years; 4-7 kg) mice are treated with large-volume phlebotomy with iron supplementation[2]
Doses: 40, 60 mg/kg Route of Administration: Po (40 mg/ kg) twice a week for 6-8 weeks Po (60 mg/kg) twice a week for 6-8 weeks Po (60 mg/kg) twice a week for 6-8 weeks Experimental Results: demonstrated reticulocytosis within 1-2 weeks of dosing. Increased total hemoglobin levels at the end of the study duration. |
| References |
[1]. Hong YR, et al. [(4-Hydroxyl-benzo[4,5]thieno[3,2-c]pyridine-3-carbonyl)-amino]-acetic acid derivatives; HIF prolyl 4-hydroxylase inhibitors as oral erythropoietin secretagogues. Bioorg Med Chem Lett. 2013 Nov 1;23(21):5953-7.
[2]. Hsieh MM, 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. [3]. Bernhardt WM, et, al. Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. J Am Soc Nephrol. 2010 Dec;21(12):2151-6. |
| Molecular Formula |
C12H9CLN2O4
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|---|---|
| Molecular Weight |
280.6639
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| CAS # |
223387-75-5
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| Related CAS # |
223387-75-5
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| SMILES |
ClC1C2=C([H])C([H])=C([H])C([H])=C2C(=C(C(N([H])C([H])([H])C(=O)O[H])=O)N=1)O[H]
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| Synonyms |
IOX3;IOX 3;IOX-3;FG-2216; FG 2216; FG2216; YM311; YM-311; YM 311.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 56 mg/mL (199.5 mM)
Water:<1 mg/mL
Ethanol:<1 mg/mL
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.91 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5630 mL | 17.8152 mL | 35.6303 mL | |
| 5 mM | 0.7126 mL | 3.5630 mL | 7.1261 mL | |
| 10 mM | 0.3563 mL | 1.7815 mL | 3.5630 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00456053 | Completed | Drug: FG2216 | Renal Anemia | FibroGen | December 2005 | Phase 2 |
Epo-induction in rhesus macques. (A) Circulating plasma Epo levels after a single oral dose of FG-2216.Blood.2007 Sep 15;110(6):2140-7. |
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Hemoglobin increases by PHI. (A) Hemoglobin (g/dL) values are presented with respect to number of days on treatment in 1 rhesus macaque treated with FG-2216 (●) and 1 control animal (○). (B) Hemoglobin levels in treated and control rhesus macaques.Blood.2007 Sep 15;110(6):2140-7. |
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COA
Blood. 2007 Sep 15;110(6):2140-7.