Details of the Drug

General Information of Drug (ID: DM5OGK0)

Drug Name

Epalrestat

Synonyms

epalrestat; 82159-09-9; Kinedak; Epalrestatum; Ono 2235; Ono-2235; Epalrestat [INN]; Epalrestatum [Latin]; ONO-2; 2-((z)-5-((e)-2-methyl-3-phenylallylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid; ONO 2; UNII-424DV0807X; C15H13NO3S2; CHEMBL56337; 5-((1Z,2E)-2-Methyl-3-phenylpropenylidene)-4-oxo-2-thioxo-3-thiazolidineacetic acid; CHEBI:31539; 5-((Z,E)-beta-Methylcinnamylidene)-4-oxo-2-thioxo-3-thiazolidineacetic acid; 424DV0807X; Epalrestatum; Aldorin (TN); Kinedak (TN); Epalrestat (JAN/INN); {5-[(E)-2-Methyl-3-phenyl-prop-2-en-(Z)-ylidene]-4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid; {(5Z)-5-[(2E)-2-methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl}acetic acid; 2-[(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid; 3-carboxymethyl-5-(methyl-3-phenylpropenylidene)rhodanine; Ono 2

Indication

Disease Entry	ICD 11	Status	REF
Diabetic neuropathy	8C0Z	Approved	[1]
Pain	MG30-MG3Z	Investigative	[2]

Therapeutic Class

Hypoglycemic Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

319.4

Topological Polar Surface Area (xlogp)

3.8

Rotatable Bond Count (rotbonds)

4

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

5

ADMET Property

MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 6.709 micromolar/kg/day [3]

Chemical Identifiers

Formula: C15H13NO3S2
IUPAC Name: 2-[(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid
Canonical SMILES: C/C(=C\\C1=CC=CC=C1)/C=C\\2/C(=O)N(C(=S)S2)CC(=O)O
InChI: 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-
InChIKey: CHNUOJQWGUIOLD-NFZZJPOKSA-N

Cross-matching ID

PubChem CID: 1549120
ChEBI ID: CHEBI:31539
CAS Number: 82159-09-9
DrugBank ID: DB15293
TTD ID: D03KOZ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aldose reductase (AKR1B1)	TTFBNVI	ALDR_HUMAN	Inhibitor	[4], [5]
Voltage-gated L-type calcium channel (L-CaC)	TTXHYV6	NOUNIPROTAC	Blocker	[2]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Diabetic neuropathy

ICD Disease Classification

8C0Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Aldose reductase (AKR1B1)	DTT	AKR1B1	1.08E-20	0.94	1.58

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

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2	Recent updates of N-type calcium channel blockers with therapeutic potential for neuropathic pain and stroke. Curr Top Med Chem. 2009;9(4):377-95.
3	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
4	Long-term effect of epalrestat, an aldose reductase inhibitor, on the development of incipient diabetic nephropathy in Type 2 diabetic patients. J Diabetes Complications. 2001 Sep-Oct;15(5):241-4.
5	Clinical investigation of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy in Japan: multicenter study. Diabetic Neuropathy Study Group in Japan. J Diabetes Complications. 1996 May-Jun;10(3):168-72.
6	Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8.
7	Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study. Diabetes Care. 2001 Oct;24(10):1776-82.
8	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2768).
9	Effect of Polygonum hydropiper sulfated flavonoids on lens aldose reductase and related enzymes. J Nat Prod. 1996 Apr;59(4):443-5.
10	ClinicalTrials.gov (NCT02332005) 12-Month Efficacy and Safety of Diepalrestat in Adults With Diabetic Peripheral Neuropathy, a DB, Placebo-Controlled Study (DE-DPN). U.S. National Institutes of Health.
11	Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors ... J Med Chem. 2005 May 5;48(9):3141-52.
12	A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report. J Diabetes Complications. 2005 Sep-Oct;19(5):247-53.
13	Effects of novel aldose reductase inhibitors, M16209 and M16287, on streptozotocin-induced diabetic neuropathy in rats. Eur J Pharmacol. 1991 Feb 7;193(2):185-91.
14	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
15	Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
16	Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
17	Effects of (S)-amlodipine and (R)-amlodipine on L-type calcium channel current of rat ventricular myocytes and cytosolic calcium of aortic smooth muscle cells. Pharmazie. 2008 Jun;63(6):470-4.
18	N- and L-type calcium channel antagonist improves glomerular dynamics, reverses severe nephrosclerosis, and inhibits apoptosis and proliferation in an l-NAME/SHR model. J Hypertens. 2002 May;20(5):993-1000.
19	Efficacy of MEM 1003, a novel calcium channel blocker, in delay and trace eyeblink conditioning in older rabbits. Neurobiol Aging. 2007 May;28(5):766-73.
20	Role of apoptosis in the kidney after reperfusion. Orv Hetil. 2008 Feb 17;149(7):305-15.
21	Hemodynamic effects of a calcium channel promoter, BAY y 5959, are preserved after chronic administration in ischemic heart failure in conscious dogs. J Pharmacol Exp Ther. 1998 Aug;286(2):760-6.
22	Q-type Ca2+ channels are located closer to secretory sites than L-type channels: functional evidence in chromaffin cells. Pflugers Arch. 1998 Mar;435(4):472-8.