| Size | Price | Stock | Qty |
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| Targets |
Sorbinil targets aldose reductase, the first and rate-limiting enzyme of the polyol pathway. In hyperglycemic conditions, excess glucose is converted to sorbitol by aldose reductase, which is then slowly metabolized to fructose by sorbitol dehydrogenase. The accumulation of sorbitol in tissues, particularly in nerves, kidneys, and the lens of the eye, is thought to contribute to the development of diabetic complications. By inhibiting aldose reductase, Sorbinil reduces the accumulation of sorbitol. This, in turn, maintains the myo-inositol content in nerves and prevents the reduction of sodium-potassium ATPase activity, which are important for normal nerve function. Sorbinil's inhibition of aldose reductase is believed to improve nerve conduction velocity and prevent tissue damage associated with diabetes.
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| ln Vitro |
In vitro studies have demonstrated that Sorbinil is a potent inhibitor of aldose reductase. Its activity is typically measured using enzyme assays with purified aldose reductase. The enzyme is incubated with its substrate, glucose or glyceraldehyde, and NADPH in the presence of varying concentrations of Sorbinil. The oxidation of NADPH is measured spectrophotometrically, and the inhibition of enzyme activity is calculated. The IC50 is determined from the dose-response curve. In cell-based assays, Sorbinil has been shown to decrease the level of sorbitol in red blood cells and other cell types exposed to high glucose concentrations. These in vitro studies confirm that Sorbinil effectively inhibits aldose reductase and reduces sorbitol accumulation.
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| ln Vivo |
In vivo studies have demonstrated that Sorbinil can improve nerve function in animal models of diabetes. In diabetic rats, Sorbinil treatment has been shown to increase nerve conduction velocity, which is a measure of nerve function. It also maintains the myo-inositol content in nerves and prevents the reduction of sodium-potassium ATPase activity. These effects are attributed to the reduction of sorbitol accumulation in the nerve tissue. Clinical studies have been conducted to evaluate the efficacy of Sorbinil in diabetic patients, but the results have been mixed, and the compound has not been approved for clinical use. Sorbinil is used as a research tool to study the role of the polyol pathway in diabetic complications.
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| Enzyme Assay |
The in vitro enzyme assay for Sorbinil measures its inhibition of aldose reductase. In a typical assay, aldose reductase is purified from a suitable source (e.g., bovine lens or recombinant expression). The enzyme is incubated with its substrate (e.g., DL-glyceraldehyde or glucose) and the cofactor NADPH in the presence of varying concentrations of Sorbinil. The reaction is monitored by measuring the decrease in absorbance at 340 nm, which corresponds to the oxidation of NADPH. The inhibition of enzyme activity is calculated, and the IC50 is determined from the dose-response curve. This assay provides a direct measure of Sorbinil's potency as an aldose reductase inhibitor.
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| Cell Assay |
In vitro cell-based assays for Sorbinil are used to study its effects on the polyol pathway in cells. A common model is the use of red blood cells or other cell types (e.g., lens epithelial cells, Schwann cells) cultured in high glucose medium to induce sorbitol accumulation. The cells are treated with Sorbinil at various concentrations, and the intracellular levels of sorbitol are measured using enzymatic or chromatographic methods. The ability of Sorbinil to reduce sorbitol accumulation is assessed. In addition, the effects of Sorbinil on myo-inositol levels and sodium-potassium ATPase activity can be measured in these cells. These assays confirm that Sorbinil inhibits aldose reductase and reduces the metabolic consequences of hyperglycemia at the cellular level.
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| Animal Protocol |
In vivo animal experiments for Sorbinil are typically conducted in rodent models of diabetes, such as streptozotocin (STZ)-induced diabetic rats. In a typical study, diabetes is induced in rats by STZ injection. The animals are then treated with Sorbinil orally or by injection for a period of weeks or months. Nerve conduction velocity is measured in the sciatic nerve using electrophysiological techniques. The levels of sorbitol and myo-inositol in nerve tissue are measured by chromatography. The activity of sodium-potassium ATPase in nerve membranes is also assessed. These studies have demonstrated that Sorbinil can improve nerve function and reduce metabolic abnormalities in diabetic animals.
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| ADME/Pharmacokinetics |
Sorbinil has a molecular weight of 236.20 g/mol and a molecular formula of C11H9FN2O3. It is a solid compound. For research use, Sorbinil is typically supplied as a powder. Its solubility in water and organic solvents is not specified in the available literature. For storage, it is recommended to keep the compound at -20°C in a dry, dark environment. Pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have been studied in the context of clinical development. Sorbinil is absorbed after oral administration and is distributed to various tissues. It is metabolized in the liver and excreted in the urine.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for Sorbinil is not provided in standard product descriptions. As a compound that was investigated in clinical trials, its safety profile has been evaluated. However, specific toxicity data, such as LD50, organ toxicity, or genotoxicity, are not detailed in the available literature. In clinical studies, Sorbinil was generally well-tolerated, but some adverse effects were reported. As with all research chemicals, standard laboratory safety precautions should be followed when handling Sorbinil. Its use is limited to research applications and it is not intended for human or veterinary use.
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| References | |
| Additional Infomation |
Sorbinil is an azaspirocyclic compound with a structure comprising a monofluorinated chromanoid skeleton linked to an imidazolidinedione ring via a spirocyclic linker. It is an EC 1.1.1.21 (aldehyde reductase) inhibitor and antioxidant. It belongs to the imidazolidinedione class of compounds, specifically the chromanoids, oxaspirocyclics, azaspirocyclics, and organofluorine compounds.
Sorbinil is a research compound that was investigated for the treatment of diabetic complications, particularly diabetic neuropathy. It is an aldose reductase inhibitor that decreases the level of sorbitol in red blood cells and increases the velocity of nerve conduction. Sorbinil maintains the myo-inositol content in the nerve and prevents the reduction of sodium-potassium ATPase activity. Although Sorbinil showed promise in preclinical studies, its clinical development was not successful, and it is not currently approved for clinical use. Sorbinil is used as a research tool to study the role of the polyol pathway in diabetic complications and to develop new aldose reductase inhibitors. Its mechanism of action involves inhibiting aldose reductase, thereby reducing sorbitol accumulation and maintaining normal nerve function. |
| Molecular Formula |
C11H9FN2O3
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| Molecular Weight |
236.2024
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| Exact Mass |
236.06
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| CAS # |
68367-52-2
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| PubChem CID |
337359
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| Appearance |
White to off-white solid powder
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| Density |
1.52g/cm3
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| Index of Refraction |
1.629
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| LogP |
1.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
17
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| Complexity |
376
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1COC2=C([C@]13C(=O)NC(=O)N3)C=C(C=C2)F
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| InChi Key |
LXANPKRCLVQAOG-NSHDSACASA-N
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| InChi Code |
InChI=1S/C11H9FN2O3/c12-6-1-2-8-7(5-6)11(3-4-17-8)9(15)13-10(16)14-11/h1-2,5H,3-4H2,(H2,13,14,15,16)/t11-/m0/s1
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| Chemical Name |
(4S)-6-fluorospiro[2,3-dihydrochromene-4,5'-imidazolidine]-2',4'-dione
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| Synonyms |
Sorbinil CP-45634CP 45634
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| HS Tariff Code |
2934.99.9001
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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 : ~100 mg/mL (~423.37 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2337 mL | 21.1685 mL | 42.3370 mL | |
| 5 mM | 0.8467 mL | 4.2337 mL | 8.4674 mL | |
| 10 mM | 0.4234 mL | 2.1169 mL | 4.2337 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 |
| NCT00000159 | COMPLETED | Drug: Sorbinil | Diabetes Mellitus Diabetic Retinopathy |
National Eye Institute (NEI) | 1983-08 | Phase 3 |
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