| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
IC50: 26 nM (Aldose reductase), 33 μM (AKR1B10), 1.8 μM (V301L AKR1B10)[1]
Fidarestat targets aldose reductase, the first enzyme in the polyol pathway of glucose metabolism. It acts as a potent inhibitor, binding to the enzyme and preventing the conversion of glucose to sorbitol. By inhibiting this pathway, it reduces the accumulation of sorbitol and other polyols in tissues, which are implicated in the pathogenesis of diabetic complications such as neuropathy, nephropathy, and retinopathy. |
|---|---|
| ln Vitro |
With IC50s of 26 nM, 33 μM, and 1.8 μM for aldose reductase AKR1B10 and V301L AKR1B10, respectively, fidarestat is an aldose reductase inhibitor [1].
In vitro, fidarestat is a potent inhibitor of aldose reductase with an IC50 of 26 nM. It shows selectivity for aldose reductase over other related enzymes, such as AKR1B10, for which it has an IC50 of 33 μM. This high potency and selectivity make it a valuable tool for studying the role of aldose reductase in diabetic complications. |
| ln Vivo |
In diabetic rats, fidarestat (SNK-860; 1 or 4 mg/kg orally daily for 4 weeks) lowers the amounts of fructose and sorbitol [2].
In vivo, administration of fidarestat after breakfast was effective in significantly alleviating some symptoms of diabetic polyneuropathy. It has been studied in clinical trials for the treatment of diabetic complications. By inhibiting aldose reductase, it reduces the accumulation of sorbitol in nerves and other tissues, which may improve nerve function and alleviate symptoms. |
| Enzyme Assay |
Fidarestat is evaluated in cell-free enzymatic assays using purified aldose reductase enzyme. The compound is incubated with aldose reductase and a substrate, such as DL-glyceraldehyde, and the inhibition of enzyme activity is measured. IC50 values are determined to quantify the potency of aldose reductase inhibition. Its selectivity over other aldo-keto reductases can also be assessed.
|
| Cell Assay |
Fidarestat is assessed in cell-based assays using cells that express aldose reductase, such as lens epithelial cells or Schwann cells. Cells are treated with fidarestat, and the accumulation of sorbitol is measured under high-glucose conditions. The compound's ability to reduce sorbitol levels and prevent cellular damage is evaluated.
|
| Animal Protocol |
Fidarestat is administered orally in animal models and in clinical trials to evaluate its efficacy in treating diabetic complications. It has been studied in models of diabetic neuropathy and retinopathy. Efficacy is assessed by measuring nerve conduction velocity, retinal function, and other relevant endpoints. Its pharmacokinetic properties are also studied in vivo.
|
| ADME/Pharmacokinetics |
Fidarestat has a molecular formula of C12H10FN3O4 and a molecular weight of 279.22. Its CAS number is 136087-85-9. The compound is a solid. It should be stored under recommended conditions. It is also known as SNK-860.
|
| Toxicity/Toxicokinetics |
No detailed toxicity data is available for Fidarestat beyond its clinical trial profile. The compound is for research use only and is not intended for human therapeutic use outside of clinical trials. Its safety profile has been studied in clinical trials for diabetic complications.
|
| References |
|
| Additional Infomation |
Fidarestat is a potent and selective aldose reductase inhibitor. It is also known as SNK-860. It has been studied for the treatment of diabetic complications. The compound is not approved for clinical use.
|
| Molecular Formula |
C12H10FN3O4
|
|---|---|
| Molecular Weight |
279.2274
|
| Exact Mass |
279.065
|
| CAS # |
136087-85-9
|
| PubChem CID |
160024
|
| Appearance |
White to off-white solid powder
|
| Density |
1.6±0.1 g/cm3
|
| Index of Refraction |
1.657
|
| LogP |
-0.24
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
20
|
| Complexity |
485
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1[C@H](OC2=C([C@]13C(=O)NC(=O)N3)C=C(C=C2)F)C(=O)N
|
| InChi Key |
WAAPEIZFCHNLKK-UFBFGSQYSA-N
|
| InChi Code |
InChI=1S/C12H10FN3O4/c13-5-1-2-7-6(3-5)12(4-8(20-7)9(14)17)10(18)15-11(19)16-12/h1-3,8H,4H2,(H2,14,17)(H2,15,16,18,19)/t8-,12-/m0/s1
|
| Chemical Name |
(2S,4S)-6-fluoro-2',5'-dioxospiro[2,3-dihydrochromene-4,4'-imidazolidine]-2-carboxamide
|
| Synonyms |
SNK 860; SNK-860; SNK860
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~895.35 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 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: ≥ 2.08 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5813 mL | 17.9064 mL | 35.8128 mL | |
| 5 mM | 0.7163 mL | 3.5813 mL | 7.1626 mL | |
| 10 mM | 0.3581 mL | 1.7906 mL | 3.5813 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
