| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
Ranirestat targets aldose reductase (AR), a key enzyme in the polyol pathway. By inhibiting AR, it prevents the conversion of glucose to sorbitol, reducing the accumulation of sorbitol in tissues. This ameliorates the cellular damage associated with diabetic complications, particularly neuropathy.
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| ln Vitro |
When large doses (500 mg/dl) of glucose are added to rat erythrocytes and sciatic nerves, ranirestat concentration-dependently prevents sorbitol formation. With IC50 values of 0.010 μM and 0.041 μM, respectively, ranirestat has a similar inhibitory impact on sorbitol buildup in rat erythrocytes and sciatic nerve [1].
In vitro, ranirestat inhibits aldose reductase activity. It inhibits inflammatory responses in endothelial cells exposed to high glucose. Its potency is measured in enzyme assays and cell-based assays. It shows neuroprotective effects in cell culture models. |
| ln Vivo |
In male STD-Wistar rats, ranirestat (0.03-1.0 mg/kg; oral; once daily; for three weeks) lowers high levels of fructose and sorbitol in the sciatic nerves of rats in a dose-dependent manner without changing blood glucose levels. Additionally, ranirestat dose-dependently reduces the reductions in motor nerve conduction velocity (MNCV) brought on by STZ [1].
In vivo, ranirestat has been studied for the treatment of diabetic neuropathy. It improves nerve function and reduces ocular and renal damage in diabetic patients. It is an investigational small-molecule drug. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for ranirestat involves measuring its ability to inhibit aldose reductase activity. The enzyme is incubated with its substrate (glucose) in the presence of varying concentrations of the drug, and the reduction in product formation (sorbitol) is measured. The IC50 is determined.
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| Cell Assay |
In vitro cellular assays for ranirestat are performed on endothelial cells exposed to high glucose. The inhibition of inflammatory responses is measured by quantifying the production of inflammatory cytokines. Its neuroprotective effects are studied in neuronal cell cultures.
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| Animal Protocol |
Animal/Disease Models: Male STD-Wistar rats (12 weeks old; 260-290 g) were injected with streptozotocin (STZ) [1]
Doses: 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg /kg Route of Administration: Oral; one time/day; for 3 weeks Experimental Results: Dose-dependently diminished elevated sorbitol and fructose levels in rat sciatic nerve without affecting blood glucose levels. In vivo animal experiments for ranirestat are conducted in models of diabetic neuropathy, such as streptozotocin-induced diabetic rats. The drug is administered orally, and its effects on nerve function, nerve conduction velocity, and histological changes are assessed. |
| ADME/Pharmacokinetics |
Ranirestat has been evaluated in clinical trials and has characterized pharmacokinetic properties. It is orally bioavailable. Its half-life and metabolism have been studied in humans. It is typically stored as a powder.
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| Toxicity/Toxicokinetics |
Ranirestat has been generally well-tolerated in clinical trials. Its safety profile has been evaluated in studies for diabetic neuropathy. Common side effects may include gastrointestinal disturbances.
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| References |
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| Additional Infomation |
Ranirestat is a novel, stereoselective, and potent aldose reductase (AKR1B; EC 1.1.1.21) inhibitor with a succinimide ring in its molecular structure that undergoes a ring-opening reaction under physiological pH conditions. It has been used in clinical trials for the treatment of mild to moderate diabetic sensorimotor polyneuropathy. Drug Indications: Investigative use for the treatment of diabetic neuropathy. Mechanism of Action: Ranirestat inhibits aldose reductase, thereby inhibiting the accumulation of intracellular sorbitol, a complication of diabetes, and alleviating diabetic neuropathy. Compared to other drugs in its class, it exhibits stronger inhibitory activity and a longer duration of action. Clinical studies have shown that Ranirestat penetrates nerve tissue well, thereby dose-dependently inhibiting the accumulation of intracellular sorbitol and fructose.
Ranirestat is an investigational drug for the treatment of diabetic neuropathy. It is also known as AS-3201. It is an aldose reductase inhibitor. It is not yet an FDA-approved drug and is in clinical development. |
| Molecular Formula |
C17H11BRFN3O4
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|---|---|
| Molecular Weight |
420.1944
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| Exact Mass |
418.992
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| CAS # |
147254-64-6
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| PubChem CID |
153948
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| Appearance |
Off-white to pink solid powder
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| Density |
1.83g/cm3
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| Boiling Point |
702.7ºC at 760mmHg
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| Flash Point |
378.8ºC
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| Vapour Pressure |
1.36E-19mmHg at 25°C
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| Index of Refraction |
1.749
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| LogP |
1.527
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
689
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1C(=O)NC(=O)[C@@]12C(=O)N(C(=O)C3=CC=CN23)CC4=C(C=C(C=C4)Br)F
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| InChi Key |
QCVNMNYRNIMDKV-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C17H11BrFN3O4/c18-10-4-3-9(11(19)6-10)8-21-14(24)12-2-1-5-22(12)17(16(21)26)7-13(23)20-15(17)25/h1-6H,7-8H2,(H,20,23,25)/t17-/m1/s1
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| Chemical Name |
(R)-2'-(4-bromo-2-fluorobenzyl)-1'H-spiro[pyrrolidine-3,4'-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone
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| Synonyms |
AS-3201 SX-3201AS3201 SX3201AS 3201 SX 3201 Ranirestat.
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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 : ≥ 50 mg/mL (~118.99 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.95 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 25.0 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: ≥ 2.5 mg/mL (5.95 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 25.0 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: ≥ 2.5 mg/mL (5.95 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 | 2.3799 mL | 11.8994 mL | 23.7988 mL | |
| 5 mM | 0.4760 mL | 2.3799 mL | 4.7598 mL | |
| 10 mM | 0.2380 mL | 1.1899 mL | 2.3799 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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