| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg | |||
| 250mg | |||
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| Targets |
Lidorestat targets aldose reductase (AKR1B1), an enzyme that belongs to the aldo-keto reductase superfamily. Aldose reductase catalyzes the NADPH-dependent reduction of glucose to sorbitol, which is then oxidized to fructose by sorbitol dehydrogenase. In hyperglycemic conditions, the increased flux through the polyol pathway leads to the accumulation of sorbitol, which is poorly membrane-permeable and can cause osmotic stress, as well as the depletion of NADPH and other metabolites. These changes contribute to oxidative stress, inflammation, and tissue damage, which are hallmarks of diabetic complications. Lidorestat is a potent and selective aldose reductase inhibitor that binds to the enzyme's active site and competitively inhibits its activity. By inhibiting aldose reductase, Lidorestat reduces sorbitol accumulation and prevents the downstream effects of polyol pathway activation.
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| ln Vitro |
Lidorestat has an IC50 of 5 μM against recombinant human aldose reductase (/h/-ALR2), according to in vitro tests. With an IC50 of 27,000 μM against recombinant human aldehyde reductase (/h/-ALR1), Lidorestat has been reported to have a selectivity of /h/-ALR1//h/-ALR2 of 5400:1[1][2].
In vitro, Lidorestat exhibits potent inhibition of aldose reductase enzymatic activity. The compound's inhibitory activity is concentration-dependent, and its IC50 for aldose reductase has been characterized in enzymatic assays using purified enzyme and a fluorogenic or spectrophotometric substrate. Lidorestat is selective for aldose reductase over other aldo-keto reductases and related enzymes. In cellular assays, Lidorestat reduces sorbitol accumulation in cells cultured under high-glucose conditions, confirming its ability to inhibit aldose reductase in a cellular context. The compound's effects on oxidative stress and inflammatory markers have also been studied, showing that aldose reductase inhibition by Lidorestat can reduce the production of reactive oxygen species and pro-inflammatory cytokines in hyperglycemic conditions. |
| ln Vivo |
Lidorestat (25 mg/kg/day; oral administration; twice daily; for 6 weeks; diabetic mice) therapy decreases fructose and reduces mortality in diabetic hAR-expressing mice. And Lidorestat does not alter weight[1].
In vivo, Lidorestat has been studied in animal models of diabetic complications. In diabetic rats, administration of Lidorestat reduces sorbitol accumulation in tissues such as the sciatic nerve, retina, and kidney, which are target organs for diabetic complications. The compound also improves nerve conduction velocity (a measure of diabetic neuropathy) and reduces albuminuria (a measure of diabetic nephropathy) in diabetic animal models. In addition, Lidorestat has been shown to reduce oxidative stress and inflammation in these models. The compound has also been investigated for its potential in cancer and neurodegenerative disorders, where aldose reductase may play a role in disease pathogenesis. However, its development for these indications has been limited. |
| Enzyme Assay |
The non-cellular assay for Lidorestat involves measuring the inhibition of aldose reductase enzymatic activity using a fluorogenic or spectrophotometric assay. Recombinant human aldose reductase is incubated with a substrate (such as DL-glyceraldehyde or glucose) and NADPH in the presence of varying concentrations of Lidorestat. The oxidation of NADPH to NADP⁺ is monitored by measuring the decrease in absorbance at 340 nm, or the formation of sorbitol is measured using a coupled enzyme assay. The inhibition of aldose reductase activity by Lidorestat is calculated as a percentage of the control (without inhibitor), and the IC50 is determined from concentration-response curves. The selectivity of Lidorestat for aldose reductase over other aldo-keto reductases is assessed by performing similar assays with related enzymes.
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| Cell Assay |
The cellular assay for Lidorestat involves treating cultured cells (such as Schwann cells, retinal cells, or kidney cells) with high-glucose medium to induce polyol pathway activation. Lidorestat is added to the culture medium at various concentrations, and the accumulation of sorbitol in the cells is measured by HPLC or enzymatic assay. The reduction in sorbitol accumulation by Lidorestat is calculated. In addition, the effects of Lidorestat on oxidative stress (measured by ROS levels), inflammation (measured by cytokine levels), and cell viability are assessed. The compound's cytoprotective effects against high-glucose-induced cell damage are evaluated.
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| Animal Protocol |
Animal/Disease Models: Diabetic low -density lipoprotein (LDL) receptor-deficient [Ldlr(-/-)] mice[1]
Doses: 25 mg/kg/day Route of Administration: Oral administration; twice (two times) daily; for 6 weeks Experimental Results: Diabetic hAR-expressing mice had diminished fructose and decreased mortality. The in vivo animal studies for Lidorestat typically use streptozotocin (STZ)-induced diabetic rats or mice. Diabetes is induced by intraperitoneal injection of STZ, and after diabetes is confirmed, Lidorestat is administered orally at various doses (typically 10-100 mg/kg) daily for several weeks. Nerve conduction velocity is measured in the sciatic nerve to assess neuropathy. Urine albumin excretion is measured to assess nephropathy. Retinal histology and vascular permeability are assessed to study retinopathy. Tissue sorbitol levels are measured in the sciatic nerve, retina, and kidney. Oxidative stress and inflammatory markers are measured in tissues. The efficacy of Lidorestat is compared to that of other aldose reductase inhibitors, such as epalrestat, or to vehicle-treated controls. |
| ADME/Pharmacokinetics |
Lidorestat has a molecular weight of 376.40 g/mol and a molecular formula of C₁₈H₁₁F₃N₂O₂S. The compound is a small molecule with good solubility in DMSO and other organic solvents. It should be stored in a cool, dry place, protected from light. Its pharmacokinetic properties, including oral bioavailability and half-life, have been characterized in preclinical studies.
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| Toxicity/Toxicokinetics |
Lidorestat is generally well-tolerated in preclinical studies at therapeutically relevant doses. However, as an aldose reductase inhibitor, it may have dose-dependent side effects, including gastrointestinal disturbances. Comprehensive toxicology data are limited, and the compound has not been approved for clinical use.
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| References |
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| Additional Infomation |
Lidorestat (IDD-676) is a potent and selective aldose reductase inhibitor that has been studied for its potential in the treatment of diabetic complications, including neuropathy, nephropathy, and retinopathy. By inhibiting aldose reductase, Lidorestat reduces the accumulation of sorbitol and prevents the downstream effects of polyol pathway activation, including oxidative stress and inflammation. The compound has shown efficacy in animal models of diabetic complications and has also been investigated for its potential in cancer and neurodegenerative disorders. However, its clinical development has been limited, and it remains a research compound.
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| Molecular Formula |
C18H11F3N2O2S
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|---|---|
| Molecular Weight |
376.35
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| Exact Mass |
376.049
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| CAS # |
245116-90-9
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| PubChem CID |
157839
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.55g/cm3
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| Boiling Point |
591.4ºC at 760 mmHg
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| Melting Point |
177-178 °C
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| Flash Point |
311.4ºC
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| Vapour Pressure |
7.87E-15mmHg at 25°C
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| Index of Refraction |
1.681
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| LogP |
4.343
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
543
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KYHVTMFADJNSGS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H11F3N2O2S/c19-11-6-12(20)18-17(16(11)21)22-14(26-18)5-9-7-23(8-15(24)25)13-4-2-1-3-10(9)13/h1-4,6-7H,5,8H2,(H,24,25)
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| Chemical Name |
2-[3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid
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| Synonyms |
IDD-676 EML-676 ALN-101IDD676 EML676 ALN101
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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 (~132.86 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.53 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. Solubility in Formulation 2: ≥ 0.56 mg/mL (1.49 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 5.6 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. View More
Solubility in Formulation 3: ≥ 0.56 mg/mL (1.49 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 | 2.6571 mL | 13.2855 mL | 26.5710 mL | |
| 5 mM | 0.5314 mL | 2.6571 mL | 5.3142 mL | |
| 10 mM | 0.2657 mL | 1.3286 mL | 2.6571 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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