Epalrestat | CAS#82159-09-9 | aldose reductase inhibitor

MedKoo Cat#: 561243 | Name: Epalrestat

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. In vivo, Epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-β1, AR, α-SMA and collagen I (both mRNA and protein).

Chemical Structure

Epalrestat

CAS#82159-09-9

Theoretical Analysis

MedKoo Cat#: 561243

Name: Epalrestat

CAS#: 82159-09-9

Chemical Formula: C15H13NO3S2

Exact Mass: 319.0337

Molecular Weight: 319.34

Elemental Analysis: C, 56.41; H, 4.10; N, 4.39; O, 15.03; S, 20.08

Price and Availability

Size	Price	Availability
250mg	USD 150.00	Ready to ship
500mg	USD 250.00	Ready to ship
1g	USD 350.00	Ready to ship
2g	USD 600.00	Ready to ship
5g	USD 950.00	2 weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

Epalrestat; Kinedak; ONO-2235; ONO 2235; ONO2235; Sorbistat;

IUPAC/Chemical Name

2-[(5Z)-5-[(E)-2-Methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid

InChi Key

CHNUOJQWGUIOLD-NFZZJPOKSA-N

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-

SMILES Code

O=C(O)CN(C/1=O)C(SC1=C/C(C)=C/C2=CC=CC=C2)=S

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C23B01B27

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Epalrestat is an aldose reductase inhibitor for the treatment of diabetic neuropathy.

In vitro activity:

At 50 μM concentration, EPS (Epalrestat) showed better antioxidant activity against H2O2 (100 μM)-induced cytotoxicity, ROS formation and mitochondrial membrane damage in retinoic acid-differentiated SH-SY5Y cell line. Furthermore, this study revealed that 50 μM of EPS concentration reduced the glycogen synthase kinase-3 β (GSK3-β) expression and total tau protein level in H2O2 (100 μM)-treated cells. Reference: J Microbiol Biotechnol. 2021 Jun 28;31(6):867-874. https://pubmed.ncbi.nlm.nih.gov/33820886/

In vivo activity:

In this test, mice treated with Epalrestat took a significantly greater number of steps in 1 minute (Figure 2C) compared to the reserpine group. The swim test is known to be associated with striatal dopamine function.46 The latency to reach the platform was longer in reserpine treated mice compared to the control. Epalrestat treatment improved this parameter significantly (Figure 2D). These results indicated that Epalrestat is a potential therapeutic agent for alleviation of Parkinson's disease-like symptoms in mice. Reference: Animal Model Exp Med. 2020 Mar; 3(1): 9–21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167235/

	Solvent	mg/mL	mM
Solubility
	DMSO	14.0	43.84
	DMF	10.0	31.31
	DMF:PBS (pH 7.2) (1:1)	0.5	1.57

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 319.34 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Lingappa S, Shivakumar MS, Manivasagam T, Somasundaram ST, Seedevi P. Neuroprotective Effect of Epalrestat on Hydrogen Peroxide-Induced Neurodegeneration in SH-SY5Y Cellular Model. J Microbiol Biotechnol. 2021 Jun 28;31(6):867-874. doi: 10.4014/jmb.2101.01002. PMID: 33820886. 2. Tatsunami R, Sato K, Murao Y, Yama K, Yu Y, Ohno S, Tampo Y. Epalrestat suppresses cadmium-induced cytotoxicity through Nrf2 in endothelial cells. Exp Ther Med. 2021 Apr;21(4):393. doi: 10.3892/etm.2021.9824. Epub 2021 Feb 24. PMID: 33680115; PMCID: PMC7918249. 3. Rahman MM, Chakraborti RR, Potol MA, Abir AH, Sharmin O, Alam M, Khan MFR, Afrin R, Jannat H, Wadud R, Habib ZF. Epalrestat improves motor symptoms by reducing oxidative stress and inflammation in the reserpine induced mouse model of Parkinson's disease. Animal Model Exp Med. 2019 Dec 30;3(1):9-21. doi: 10.1002/ame2.12097. PMID: 32318655; PMCID: PMC7167235. 4. Yang BB, Hong ZW, Zhang Z, Yu W, Song T, Zhu LL, Jiang HS, Chen GT, Chen Y, Dai YT. Epalrestat, an Aldose Reductase Inhibitor, Restores Erectile Function in Streptozocin-induced Diabetic Rats. Int J Impot Res. 2019 Mar;31(2):97-104. doi: 10.1038/s41443-018-0075-x. Epub 2018 Sep 13. Erratum in: Int J Impot Res. 2019 Feb 4;: PMID: 30214006; PMCID: PMC6462873.

In vitro protocol:

In vivo protocol:

1. Rahman MM, Chakraborti RR, Potol MA, Abir AH, Sharmin O, Alam M, Khan MFR, Afrin R, Jannat H, Wadud R, Habib ZF. Epalrestat improves motor symptoms by reducing oxidative stress and inflammation in the reserpine induced mouse model of Parkinson's disease. Animal Model Exp Med. 2019 Dec 30;3(1):9-21. doi: 10.1002/ame2.12097. PMID: 32318655; PMCID: PMC7167235. 2. Yang BB, Hong ZW, Zhang Z, Yu W, Song T, Zhu LL, Jiang HS, Chen GT, Chen Y, Dai YT. Epalrestat, an Aldose Reductase Inhibitor, Restores Erectile Function in Streptozocin-induced Diabetic Rats. Int J Impot Res. 2019 Mar;31(2):97-104. doi: 10.1038/s41443-018-0075-x. Epub 2018 Sep 13. Erratum in: Int J Impot Res. 2019 Feb 4;: PMID: 30214006; PMCID: PMC6462873.

1: Bailly C. Moving toward a new horizon for the aldose reductase inhibitor epalrestat to treat drug-resistant cancer. Eur J Pharmacol. 2022 Sep 15;931:175191. doi: 10.1016/j.ejphar.2022.175191. Epub 2022 Aug 11. PMID: 35964660. 2: Vishwakarma VK, Paswan SK, Arora T, Verma RK, Yadav HN. Pain Allaying Epalrestat-Loaded Lipid Nanoformulation for the Diabetic Neuropathic Pain Interventions: Design, Development, and Animal Study. Curr Drug Metab. 2022;23(7):571-583. doi: 10.2174/1389200223666220810152633. PMID: 35950248. 3: Zhu Y, Sheng Y. Retraction notice to "Sustained delivery of epalrestat to the retina using PEGylated solid lipid nanoparticles laden contact lens" [Int. J. Pharm. 587 (2020) 119688]. Int J Pharm. 2022 Aug 25;624:122033. doi: 10.1016/j.ijpharm.2022.122033. Epub 2022 Jul 20. PMID: 35870291. 4: Zhou Y, Wang R, Han F, Zhang J. Efficacy of epalrestat combined with alprostadil for diabetic nephropathy and its impacts on renal fibrosis and related factors of inflammation and oxidative stress. Am J Transl Res. 2022 May 15;14(5):3172-3179. PMID: 35702110; PMCID: PMC9185026. 5: Kulkarni UD, Kumari Kamalkishore M, Vittalrao AM, Kumar Siraganahalli Eshwaraiah P. Cognition enhancing abilities of vitamin D, epalrestat and their combination in diabetic rats with and without scopolamine induced amnesia. Cogn Neurodyn. 2022 Apr;16(2):483-495. doi: 10.1007/s11571-021-09718-6. Epub 2021 Sep 15. PMID: 35401868; PMCID: PMC8934839. 6: Alvi Z, Akhtar M, Mahmood A, Ur-Rahman N, Nazir I, Sadaquat H, Ijaz M, Syed SK, Waqas MK, Wang Y. Enhanced Oral Bioavailability of Epalrestat SBE7-β-CD Complex Loaded Chitosan Nanoparticles: Preparation, Characterization and in-vivo Pharmacokinetic Evaluation. Int J Nanomedicine. 2021 Dec 29;16:8353-8373. doi: 10.2147/IJN.S339857. PMID: 35002232; PMCID: PMC8721161. 7: Alvi Z, Akhtar M, Rahman NU, Hosny KM, Sindi AM, Khan BA, Nazir I, Sadaquat H. Utilization of Gelling Polymer to Formulate Nanoparticles Loaded with Epalrestat-Cyclodextrin Inclusion Complex: Formulation, Characterization, In- Silico Modelling and In-Vivo Toxicity Evaluation. Polymers (Basel). 2021 Dec 12;13(24):4350. doi: 10.3390/polym13244350. PMID: 34960901; PMCID: PMC8708980. 8: Sato K, Tatsunami R, Wakame K. Epalrestat suppresses inflammatory response in lipopolysaccharide-stimulated RAW264.7 cells. Allergol Immunopathol (Madr). 2021 Sep 1;49(5):1-8. doi: 10.15586/aei.v49i5.102. PMID: 34476915. 9: Lingappa S, Shivakumar MS, Manivasagam T, Somasundaram ST, Seedevi P. Neuroprotective Effect of Epalrestat on Hydrogen Peroxide-Induced Neurodegeneration in SH-SY5Y Cellular Model. J Microbiol Biotechnol. 2021 Jun 28;31(6):867-874. doi: 10.4014/jmb.2101.01002. PMID: 33820886; PMCID: PMC9705952. 10: Elmazoglu Z, Prnova MS, Stefek M, Ceylan AF, Aschner M, Rangel-López E, Santamaria A, Karasu C. Protective Effects of Novel Substituted Triazinoindole Inhibitors of Aldose Reductase and Epalrestat in Neuron-like PC12 Cells and BV2 Rodent Microglial Cells Exposed to Toxic Models of Oxidative Stress: Comparison with the Pyridoindole Antioxidant Stobadine. Neurotox Res. 2021 Jun;39(3):588-597. doi: 10.1007/s12640-021-00349-7. Epub 2021 Mar 13. PMID: 33713301. 11: Tatsunami R, Sato K, Murao Y, Yama K, Yu Y, Ohno S, Tampo Y. Epalrestat suppresses cadmium-induced cytotoxicity through Nrf2 in endothelial cells. Exp Ther Med. 2021 Apr;21(4):393. doi: 10.3892/etm.2021.9824. Epub 2021 Feb 24. PMID: 33680115; PMCID: PMC7918249. 12: Choudhary S, Silakari O. Virtual screening of epalrestat mimicking selective ALR2 inhibitors from natural product database: auto pharmacophore, ADMET prediction and molecular dynamics approach. J Biomol Struct Dyn. 2022 Aug;40(13):6052-6070. doi: 10.1080/07391102.2021.1875878. Epub 2021 Jan 22. PMID: 33480327. 13: Choudhary S, Kumar M, Silakari O. QM/MM analysis, synthesis and biological evaluation of epalrestat based mutual-prodrugs for diabetic neuropathy and nephropathy. Bioorg Chem. 2021 Mar;108:104556. doi: 10.1016/j.bioorg.2020.104556. Epub 2020 Dec 15. PMID: 33376013. 14: Tatsunami R, Murao Y, Sato K. [Protective Effect of Epalrestat against Oxidative Stress-induced Cytotoxicity]. Yakugaku Zasshi. 2020;140(11):1381-1388. Japanese. doi: 10.1248/yakushi.20-00167. PMID: 33132274. 15: Ji J, Xu MX, Qian TY, Zhu SZ, Jiang F, Liu ZX, Xu WS, Zhou J, Xiao MB. The AKR1B1 inhibitor epalrestat suppresses the progression of cervical cancer. Mol Biol Rep. 2020 Aug;47(8):6091-6103. doi: 10.1007/s11033-020-05685-z. Epub 2020 Aug 5. PMID: 32761301. 16: Zhu Y, Sheng Y. Sustained delivery of epalrestat to the retina using PEGylated solid lipid nanoparticles laden contact lens. Int J Pharm. 2020 Sep 25;587:119688. doi: 10.1016/j.ijpharm.2020.119688. Epub 2020 Jul 25. Retraction in: Int J Pharm. 2022 Aug 25;624:122033. PMID: 32717281. 17: Geng N, Jin Y, Li Y, Zhu S, Bai H. AKR1B10 Inhibitor Epalrestat Facilitates Sorafenib-Induced Apoptosis and Autophagy Via Targeting the mTOR Pathway in Hepatocellular Carcinoma. Int J Med Sci. 2020 May 18;17(9):1246-1256. doi: 10.7150/ijms.42956. PMID: 32547320; PMCID: PMC7294918. 18: Rahman MM, Chakraborti RR, Potol MA, Abir AH, Sharmin O, Alam M, Khan MFR, Afrin R, Jannat H, Wadud R, Habib ZF. Epalrestat improves motor symptoms by reducing oxidative stress and inflammation in the reserpine induced mouse model of Parkinson's disease. Animal Model Exp Med. 2019 Dec 30;3(1):9-21. doi: 10.1002/ame2.12097. PMID: 32318655; PMCID: PMC7167235. 19: Sun H, Liu S, Gao X, Xiong Z, He Z, Zhao L. Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS. J Pharm Anal. 2019 Dec;9(6):423-430. doi: 10.1016/j.jpha.2018.08.002. Epub 2018 Aug 15. PMID: 31890342; PMCID: PMC6931074. 20: Iyer S, Sam FS, DiPrimio N, Preston G, Verheijen J, Murthy K, Parton Z, Tsang H, Lao J, Morava E, Perlstein EO. Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG. Dis Model Mech. 2019 Nov 11;12(11):dmm040584. doi: 10.1242/dmm.040584. PMID: 31636082; PMCID: PMC6899038.

View History

LSP4-2022

MedKoo CAT#: 532124

CAS#: 1413405-33-0