FG-4592 (ASP1517)
FG-4592 (also known as ASP1517), 2-(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxamido)acetic acid, is a potent small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), an enzyme up-regulating the expression of endogenous human erythropoietin (Epo). It is currently being investigated as an oral treatment for anemia associated with chronic kidney disease (CKD). Unlike other anemia treating agents, erythropoiesis-stimulating agents (ESAs), FG-4592 inhibits HIF, through a distinctive mechanism, by stabilization of HIF. According to previous studies, FG-4592 is capable of correcting and maintaining hemoglobin levels in CKD patients not receiving dialysis and in patients of end-stage renal disease who receives dialysis but do not need intravenous iron supplement.
Reference
1. Luis Borges. Different modalities of erythropoiesis stimulating agents. Port J Nephrol Hypert 2010; 24(2): 137-145
2. “FibroGen and Astellas announce initiation of phase 3 trial of FG-4592/ASP1517 for treatment of anemia of chronic kidney disease” Fibrogen Press Release. Dec 11 2012
3. “FibroGen announces initiation of phase 2b studies of FG-4592, an oral HIF prolyl hydroxylase inhibitor, for treatment of anemia”
- 1. Nicholson HE, Tariq Z, et al. "HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species." Sci Signal. 2019 Oct 1;12(601). pii: eaay0482. PMID:31575731
- 2. LUKE ERBER. "Functional Proteomics Analysis To Discover And Characterize Oxygen-Dependent Cellular Pathways." UNIVERSITY OF MINNESOTA. 2019.
- 3. Kiriakidis S, Hoer SS, et al. "Complement C1q is hydroxylated by collagen prolyl 4 hydroxylase and is sensitive to off-target inhibition by prolyl hydroxylase domain inhibitors that stabilize hypoxia-inducible factor." Kidney Int. 2017 May 12. pii: S0085-2538(17)30180-1. PMID:28506759
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 352.34 |
| Cas No. | 808118-40-3 |
| Formula | C19H16N2O5 |
| Solubility | insoluble in H2O; ≥17.62 mg/mL in DMSO; ≥2.9 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | 2-[(4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid |
| SDF | Download SDF |
| Canonical SMILES | CC1=NC(=C(C2=C1C=C(C=C2)OC3=CC=CC=C3)O)C(=O)NCC(=O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
|
Cell lines |
PC-12 cells |
|
Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
|
Reaction Conditions |
5, 20 or 50 μM |
|
Applications |
FG-4592 showed significant protection effect against the TBHP-induced cell death. |
| Animal experiment [1]: | |
|
Animal models |
Mouse model of spinal cord injury |
|
Dosage form |
50mg/kg/day; i.p.; for 7 days |
|
Applications |
In a mouse model of spinal cord injury, FG-4592 administration improved recovery and increased the survival of neurons in spinal cord lesions. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Wu K, Zhou K, Wang Y, Zhou Y, Tian N, Wu Y, Chen D, Zhang D, Wang X, Xu H, Zhang X. Stabilization of HIF-1α by FG-4592 promotes functional recovery and neural protection in experimental spinal cord injury. Brain Res. 2016 Feb 1;1632:19-26. |
|
| Description | FG-4592 is an inhibitor of HIF α prolyl hydroxylase. | |||||
| Targets | HIF α prolyl hydroxylase | |||||
| IC50 | ||||||
Quality Control & MSDS
- View current batch:
Chemical structure
Related Biological Data
Related Biological Data
