| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
Aldose reductase (AR), also known as AKR1B1. Zopolrestat is a potent inhibitor of aldose reductase with an IC50 of 3.1 nM. It also inhibits the related enzyme AKR1B10, which has been implicated in inflammation and cancer. By inhibiting aldose reductase, Zopolrestat prevents the accumulation of sorbitol in tissues, which is a key mechanism in the development of diabetic complications.
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| ln Vitro |
Zopolrestat is an effective inhibitor of human and rat enzymes that degrade glyceraldehyde and glucose [1].
Zopolrestat demonstrates potent inhibitory activity against aldose reductase with IC50 values reported as 3.1 nM, with some sources reporting IC50s of 1.9 nM and 41 nM depending on the assay conditions. The compound effectively prevents sorbitol accumulation in tissues, which is the primary mechanism underlying its potential therapeutic effects in diabetic complications. It has been evaluated in various in vitro and in vivo experimental models of diabetic complications. |
| ln Vivo |
In diabetic rats, zoleprestat (oral; 2.5 mg/kg–50 mg/kg; once daily for 5 days, followed by 7 days of recovery) enhances galactosemia and normalizes renal blood flow while preventing sorbitol accumulation in the renal cortex [1].
In diabetic rats, Zopolrestat (oral administration at 2.5 mg/kg to 50 mg/kg once daily for 5 days followed by 7 days of recovery) enhances galactosemia and normalizes renal blood flow while preventing sorbitol accumulation in the renal cortex. It also restores antigen-induced protein extravasation and mast cell degranulation in diabetic sensitized rats. These findings suggest that Zopolrestat can ameliorate diabetic complications in preclinical models. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for Zopolrestat typically involves measuring the activity of recombinant aldose reductase using a standard spectrophotometric assay. The enzyme is incubated with the substrate (DL-glyceraldehyde or glucose) and NADPH as a cofactor, and the decrease in NADPH absorbance is monitored at 340 nm. The compound is tested at various concentrations to determine the IC50 value. Inhibition of AKR1B10 can also be assessed using similar methods.
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| Cell Assay |
The in vitro cellular assay for Zopolrestat typically involves culturing cells that express aldose reductase, such as lens epithelial cells, Schwann cells, or endothelial cells. Cells are cultured in high-glucose medium to induce sorbitol accumulation, and the compound is added at various concentrations. The intracellular sorbitol levels are measured using enzymatic or chromatographic methods to assess the inhibitory effect of the compound on aldose reductase activity in the cellular context.
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| Animal Protocol |
Animal/Disease Models: Male SD (Sprague-Dawley) rats (made diabetic by iv injection of streptozotocin)[1].
Doses: 2.5 mg/kg-50 mg/kg Route of Administration: Po; once-a-day for 5 days Experimental Results: Its ED50s in reversing already elevated sorbitol accumulation in rat sciatic nerve, retina, and lens in a chronic test were 1.9, 17.6, and 18.4 mg/kg, respectively. In vivo animal studies for Zopolrestat typically involve the use of diabetic rat models, such as streptozotocin-induced or alloxan-induced diabetic rats. Rats are administered the compound via oral gavage at doses ranging from 2.5 mg/kg to 50 mg/kg. Endpoints include measurement of sorbitol accumulation in tissues (e.g., renal cortex, lens, nerve), assessment of renal blood flow, and evaluation of diabetic complications such as neuropathy and nephropathy. |
| ADME/Pharmacokinetics |
Zopolrestat is orally active with favorable pharmacokinetic properties. It has a molecular weight of 419.38 g/mol and a molecular formula of C19H12F3N3O3S. The compound has been evaluated in tissue distribution and biotransformation studies in rats using 14C-labeled Zopolrestat. Water-soluble salts of Zopolrestat have been developed to improve its solubility and bioavailability.
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| Toxicity/Toxicokinetics |
Specific toxicology data for Zopolrestat are not extensively reported in the public domain. The compound is intended for research use only. In preclinical studies, it has been administered to rats at various doses without reported severe toxicity. Comprehensive toxicity studies would be required before any clinical application. Researchers should consult the safety data sheet for detailed handling information.
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| References | |
| Additional Infomation |
Zopolrestat is also known as CP73850 and is an aldose reductase inhibitor that has been investigated for the treatment of diabetic complications. It is also known by the Chinese name 唑泊司他. The compound has been the subject of patents related to water-soluble salts for improved formulation. It has not yet received regulatory approval and is strictly for preclinical research purposes. The molecular formula is C19H12F3N3O3S.
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| Molecular Formula |
C19H12F3N3O3S
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| Molecular Weight |
419.3782
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| Exact Mass |
419.055
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| CAS # |
110703-94-1
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| PubChem CID |
1613
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| Appearance |
White to off-white solid powder
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| Density |
1.58g/cm3
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| Boiling Point |
598.7ºC at 760mmHg
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| Flash Point |
315.9ºC
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| Vapour Pressure |
3.5E-15mmHg at 25°C
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| Index of Refraction |
1.683
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
702
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BCSVCWVQNOXFGL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H12F3N3O3S/c20-19(21,22)10-5-6-15-14(7-10)23-16(29-15)9-25-18(28)12-4-2-1-3-11(12)13(24-25)8-17(26)27/h1-7H,8-9H2,(H,26,27)
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| Chemical Name |
2-(4-oxo-3-((5-(trifluoromethyl)benzo[d]thiazol-2-yl)methyl)-3,4-dihydrophthalazin-1-yl)acetic acid
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| Synonyms |
CP-73850 CP73850 CP 73850
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~238.45 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (1.98 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 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 0.83 mg/mL (1.98 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 8.3 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: ≥ 0.83 mg/mL (1.98 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 20 mg/mL (47.69 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3845 mL | 11.9224 mL | 23.8447 mL | |
| 5 mM | 0.4769 mL | 2.3845 mL | 4.7689 mL | |
| 10 mM | 0.2384 mL | 1.1922 mL | 2.3845 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.
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