FG-4592 (ASP1517) is a novel Hypoxia Inducible Factor Prolyl Hydroxylase inhibitor, in CKD Anemia. FG-4592 is an oral inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylase in clinical development for the treatment of anemia. Stabilization of HIF, a cytosolic transcription factor, by FG-4592 leads to activation of the genes associated with erythropoiesis, including EPO and enzymes involved in iron metabolism.
|Source||Hypoxia (2015). Figure 4. FG-4592|
|Cell Lines||FVB mice|
|Concentrations||40 and 80 mg/kg|
|Incubation Time||104, 99.5, and 102 days|
|Results||At this time-point, roxadustat induced a substantial increase in circulating EPO protein (33×), whereas VEGF levels appeared unaffected by treatment.|
|Cell lines||PC12 cells|
|Preparation method||Cell viability assay Cell viability was assayed using the Cell Counting Kit-8 (CCK-8; Dojindo Co., Kumamoto, Japan) according to the manufacture's protocol. Briefly, PC12 Cells were planted in 96-well plates at a density of 5000 cells per cm2 and incubated at 37 ℃ in a 5% CO2 humidified atmosphere for 24 h. Then the cells were treated with TBHP, FG-4592 and YC-1 as described above. After treatment the cells were washed with PBS, then 100 μL of DMEM and 10 μL of CCK-8 solution was added to each well of 96-well plates, and the plates was incubated for an additional 1 h. The absorbance was then measured at the wavelength of 450 nm by a microplate reader to assess the number of viable cells.|
|Animal models||SCI recovery mice model|
|Formulation||100 mg FG-4592 was dissolved to 9.675 mL of 5% Dextrose and 325 mL of 1 N NaOH|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 70 mg/mL|
Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis.
Beuck S, et al. Drug Test Anal. 2012 Nov;4(11):830-45. PMID: 22362605.
|Related HIF Products|
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PT2385 is an orally active, selective inhibitor of hypoxia inducible factor (HIF)-2alpha, with a Ki value of less than 50 nM.
JNJ-42041935 is a potent, competitive, reversible, and selective inhibitor of PHD with pKi values of 7.91±0.04, 7.29 ±0.05, and 7.65±0.09 for PHD1, PHD2, and PHD3, respectively.
Daprodustat (GSK1278863) is a novel, orally active HIF-prolyl hydroxylase inhibitor.
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