| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Epalrestat (formerly also named ONO-2235) is a novel and potent aldose reductase inhibitor used for the treatment of diabetic neuropathy. It may affect or delay progression of the underlying disease process. Data from six clinical trials were evaluated, and it was determined that epalrestat 50 mg 3 times/day may improve motor and sensory nerve conduction velocity and subjective neuropathy symptoms as compared with baseline and placebo. Epalrestat may serve as a new therapeutic option to prevent or slow the progression of diabetic neuropathy. Epalrestat significantly increased the amplitude of 3 cpm waves on EGG and improved the spectral analytical parameters of heart rate variability. These findings suggest that epalrestat is useful for the treatment of diabetic gastroparesis. Epalrestat is a highly effective and safe agent for the treatment of diabetic neuropathy.
| Targets |
Aldose reductase
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| ln Vitro |
In Schwann cells (SC), epalrestat (100 and 200 µM, 24 hours) adsorbs cell viability and causes cell fluorescence [5]. Epalrestat activates Nrf2 to upregulate γ-GCS throughout a 24-hour period at 10 and 50 µM. The SC epoxy levels are protected by epalrestat (50 µM, 16 hours) [5].
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| ln Vivo |
For eight weeks, epalrestat (0.08% (w/w) in a regular feed) protected against nephritis in diabetic nephropathy with a db/db ratio [4]. Epalrestat (100 mg/kg i.g. daily for 6 weeks). shields the scaffold against the damage caused by streptozotocin (streptozotocin) to diabetic peripheral nerves (DPN) [6]. The mouse brain's infarct volume and blood-brain barrier permeability can be decreased by epalrestat (50 mg/kg, given twice a day through the appendix) [7].
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| Cell Assay |
RT-PCR[5]
Cell Types: rat SCs, thereby increasing intracellular glutamine in SC[5]. Tested Concentrations: 10 or 50 µM Incubation Duration: 4 hrs (hours) Experimental Results: At 10 and 50 µM concentrations, nuclear levels of active Nrf2 increased 1.8- and 3.8-fold, but failed to increase Nrf2 mRNA levels. |
| Animal Protocol |
Animal/Disease Models: db/db mice[4]
Doses: 0.08% (w/w) fed regular feed Doses: 8 weeks Experimental Results: Improved GBM thickening and mesangial matrix deposition in renal tissue. Reduces elevated sorbitol and fructose in plasma, urine, and renal cortex of db/db mice. Myo-inositol diminished in plasma and urine, whereas it increased in the renal cortex. Animal/Disease Models: Rats were fed a high-fat and high-sugar diet for 4 weeks, and streptozotocin was injected at the 4th and 8th weeks [6] Doses: 100 mg/kg/d Route of Administration: ig for 6 weeks Experimental Results: Improved pathological structure of rats Neurites and myelin. SOD, CAT, and GPX protein levels were increased in the sciatic nerve. Reduces aldose reductase levels in the sciatic nerve. |
| Toxicity/Toxicokinetics |
rat LD50 oral 5300 ug/kg Iyakuhin Kenkyu. Study of Medical Supplies., 23(201), 1992
rat LD50 intraperitoneal 922 gm/kg Iyakuhin Kenkyu. Study of Medical Supplies., 23(201), 1992 rat LD50 subcutaneous >3 gm/kg Iyakuhin Kenkyu. Study of Medical Supplies., 23(201), 1992 rat LD50 intravenous 255 ug/kg Iyakuhin Kenkyu. Study of Medical Supplies., 23(201), 1992 mouse LD50 oral 3200 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 23(201), 1992 |
| References |
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| Additional Infomation |
Epalrestat is a monocarboxylic acid that is 1,3-thiazolidine which is substituted on the nitrogen by a carboxymethyl group, at positions 2 and 4 by thioxo and oxo groups, respectively, and at position 5 by a 2-methyl-3-phenylprop-2-en-1-ylidene group. It is an inhibitor of aldose reductase (which catalyses the conversion of glucose to sorbitol) and is used for the treatment of some diabetic complications, including neuropathy. It has a role as an EC 1.1.1.21 (aldehyde reductase) inhibitor. It is a member of thiazolidines and a monocarboxylic acid.
Epalrestat is under investigation in clinical trial NCT03244358 (Evaluation of Epalrestat in Metastatic Triple-negative Breast Cancer). Epalrestat is an orally available, a non-competitive, reversible inhibitor of aldose reductase (AR), with potential antineoplastic, antioxidant, and anti-inflammatory activities. Upon oral administration, epalrestat non-competitively binds to AR, a polyol pathway enzyme that catalyzes reactive oxygen species (ROS)-initiated lipid peroxidation-generated lipid aldehydes and their glutathione conjugates, which have been implicated in the activation of transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) and activator protein-1 (AP-1), which control the transcription of many inflammatory cytokines. Increased inflammatory cytokines and growth factors promote cell proliferation, a primary feature in the tumorigenesis process. AR is overexpressed in several oxidative stress- and inflammation-related conditions, including cancer. |
| Molecular Formula |
C15H13NO3S2
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| Molecular Weight |
319.4
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| Exact Mass |
319.033
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| Elemental Analysis |
C, 56.41; H, 4.10; N, 4.39; O, 15.03; S, 20.08
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| CAS # |
82159-09-9
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| Related CAS # |
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| PubChem CID |
1549120
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| Appearance |
Pink to red solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
516.8±60.0 °C at 760 mmHg
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| Melting Point |
210-217ºC
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| Flash Point |
266.4±32.9 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.706
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| LogP |
2.02
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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 |
4
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| Heavy Atom Count |
21
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| Complexity |
519
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C/C(=C\C1=CC=CC=C1)/C=C\2/C(=O)N(C(=S)S2)CC(=O)O
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| InChi Key |
CHNUOJQWGUIOLD-NFZZJPOKSA-N
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| InChi Code |
InChI=1S/C15H13NO3S2/c1-10(7-11-5-3-2-4-6-11)8-12-14(19)16(9-13(17)18)15(20)21-12/h2-8H,9H2,1H3,(H,17,18)/b10-7+,12-8-
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| Chemical Name |
2-[(5Z)-5-[(E)-2-Methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid
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| Synonyms |
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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. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1309 mL | 15.6544 mL | 31.3087 mL | |
| 5 mM | 0.6262 mL | 3.1309 mL | 6.2617 mL | |
| 10 mM | 0.3131 mL | 1.5654 mL | 3.1309 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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