General Information of Drug (ID: DMSUFW6)

Drug Name
SSR-125047
Synonyms
Tolrestat; TOLRESTAT; 82964-04-3; Alredase; Lorestat; Tolrestatin; Tolrestatum; Tolrestatum [Latin]; AY-27773; 2-(6-Methoxy-N-methyl-5-(trifluoromethyl)naphthalene-1-carbothioamido)acetic acid; UNII-0T93LG5NMK; AY 27773; AY-27,773; CHEMBL436; 0T93LG5NMK; CHEBI:48549; LUBHDINQXIHVLS-UHFFFAOYSA-N; N-{[6-methoxy-5-(trifluoromethyl)naphthalen-1-yl]carbonothioyl}-N-methylglycine; NCGC00183862-01; N-(6-Methoxythio-5-(trifluoromethyl)-1-naphthoyl)sarcosine; N-{[6-methoxy-5-(trifluoromethyl)-1-naphthyl]carbonothioyl}-N-methylglycine
Indication
Disease Entry ICD 11 Status REF
Schizophrenia 6A20 Phase 1 [1]
Diabetic cataract 9B10.21 Withdrawn from market [2], [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 357.3
Topological Polar Surface Area (xlogp) 3.7
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 8 micromolar/kg/day [5]
Chemical Identifiers
Formula
C16H14F3NO3S
IUPAC Name
2-[[6-methoxy-5-(trifluoromethyl)naphthalene-1-carbothioyl]-methylamino]acetic acid
Canonical SMILES
CN(CC(=O)O)C(=S)C1=CC=CC2=C1C=CC(=C2C(F)(F)F)OC
InChI
InChI=1S/C16H14F3NO3S/c1-20(8-13(21)22)15(24)11-5-3-4-10-9(11)6-7-12(23-2)14(10)16(17,18)19/h3-7H,8H2,1-2H3,(H,21,22)
InChIKey
LUBHDINQXIHVLS-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
53359
ChEBI ID
CHEBI:48549
CAS Number
82964-04-3
DrugBank ID
DB02383
TTD ID
D0Q7QY

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 [6]
Opioid receptor sigma 1 (OPRS1) TT5TPI6 SGMR1_HUMAN Binder [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Schizophrenia
ICD Disease Classification 6A20
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Opioid receptor sigma 1 (OPRS1) DTT SIGMAR1 2.77E-06 -0.12 -0.62
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
2 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. (Ligand id: 7404).
3 Effect of tolrestat, an aldose reductase inhibitor, on neutrophil respiratory burst activity in diabetic patients. Metabolism. 1997 Jun;46(6):634-8.
4 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
5 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
6 Aldose reductase inhibitors: an update. Ann Pharmacother. 1993 Jun;27(6):751-4.
7 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.
8 Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8.
9 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.
10 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).
11 Effect of Polygonum hydropiper sulfated flavonoids on lens aldose reductase and related enzymes. J Nat Prod. 1996 Apr;59(4):443-5.
12 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.
13 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.
14 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.
15 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.
16 Dextromethorphan/quinidine: AVP 923, dextromethorphan/cytochrome P450-2D6 inhibitor, quinidine/dextromethorphan. Drugs R D. 2005;6(3):174-7.
17 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
18 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
19 Antitussives and substance abuse. Subst Abuse Rehabil. 2013 Nov 6;4:75-82.
20 Clinical pipeline report, company report or official report of SK BioPhamaceuticals.
21 Antiamnesic and neuroprotective effects of donepezil against learning impairments induced in mice by exposure to carbon monoxide gas. J Pharmacol Exp Ther. 2006 Jun;317(3):1307-19.
22 Antidepressant-like responses to the combined sigma and 5-HT1A receptor agonist OPC-14523. Neuropharmacology. 2001 Dec;41(8):976-88.
23 2011 Pipeline of Anavex.
24 Tumor imaging with 2 sigma-receptor ligands, 18F-FE-SA5845 and 11C-SA4503: a feasibility study. J Nucl Med. 2004 Nov;45(11):1939-45.
25 SSR125329A, a high affinity sigma receptor ligand with potent anti-inflammatory properties. Eur J Pharmacol. 2002 Dec 5;456(1-3):123-31.