Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM5OGK0)

• Drug Name: Epalrestat Drug Info
• 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
• Cross-matching ID:
  PubChem CID: 1549120
  ChEBI ID: CHEBI:31539
  CAS Number: CAS 82159-09-9
  TTD Drug ID: DM5OGK0

Molecule-Related Drug Atlas

Drug(s) Targeting Aldose reductase (AKR1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sulindac	DM2QHZU	Rheumatoid arthritis	FA20	Approved	[5]
Fidarestat	DMZL1I8	Diabetic complication	5A2Y	Phase 3	[6]
Ranirestat	DMD5QRS	Diabetic neuropathy	8C0Z	Phase 3	[7]
Contigoside B	DMX9V8K	Thrombosis	DB61-GB90	Phase 2/3	[8]
BNV-222	DMYFQJL	Diabetic neuropathy	8C0Z	Phase 2/3	[9]
LIDORESTAT	DMA0RI9	Diabetic complication	5A2Y	Phase 2	[10]
QR-333	DMKVIWM	Diabetic neuropathy	8C0Z	Phase 2	[11]
ADMVA	DM819CO	Diabetic complication	5A2Y	Phase 2	[7]
M-16209	DMZ7YX3	Diabetic complication	5A2Y	Phase 2	[12]
T2c-003	DMWIH59	Diabetic neuropathy	8C0Z	Phase 1/2	[7]

Drug(s) Targeting Voltage-gated L-type calcium channel (L-CaC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[13]
Clevidipine butyrate	DMW4M97	Hypertension	BA00-BA04	Approved	[14]
Otilonium bromide	DM05968	Gastric motility disorder	DA21	Approved	[15]
Levamlodipine	DM92S6N	Hypertension	BA00-BA04	Phase 4	[16]
Cilnidipine	DM1975O	High blood pressure	BA00	Phase 3	[17]
Pinaverium bromide	DM7OSHC	Irritable bowel syndrome	DD91.0	Phase 3	[15]
MEM-1003	DMYZU6G	Bipolar disorder	6A60	Phase 2a	[18]
Gallopamil	DMXBR27	Asthma	CA23	Phase 2	[19]
BAY-Y-5959	DMLO18H	Cardiovascular disease	BA00-BE2Z	Phase 2	[20]
Furnidipine	DME94QF	Nerve injury	ND56.4	Discontinued in Phase 3	[21]

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	[3] , [4]
Voltage-gated L-type calcium channel (L-CaC)	TTXHYV6	NOUNIPROTAC	Blocker	[2]

References

• [1] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [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] 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.
• [4] 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.
• [5] Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8.
• [6] 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.
• [7] 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).
• [8] Effect of Polygonum hydropiper sulfated flavonoids on lens aldose reductase and related enzymes. J Nat Prod. 1996 Apr;59(4):443-5.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [14] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [15] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Role of apoptosis in the kidney after reperfusion. Orv Hetil. 2008 Feb 17;149(7):305-15.
• [20] 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.
• [21] 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.