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.
|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|
|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.|
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|
|Molidustat (BAY 85-3934)
Molidustat (BAY 85-3934) is a potent hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor with IC50 of 480 nM, 280 nM, and 450 nM for PHD1, PHD2, and PHD, respectively. Phase 2.
MK-8617 is an orally active pan-inhibitor of Hypoxia-inducible factor prolyl hydroxylase 1−3 (HIF PHD1−3), inhibiting PHD1, 2, 3 with IC50s of 1.0, 1.0 and 14 nM, respectively.
PX-478 2HCl is an orally active, and selective hypoxia-inducible factor-1α (HIF-1α) inhibitor.
BAY 87-2243 is a potent and selective hypoxia-inducible factor-1 (HIF-1) inhibitor.
Chlorogenic Acid is an analog of caffeic acid that displays antioxidant, analgesic, antipyretic and chemopreventive activity.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.