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

General Information of Drug (ID: DMZL1I8)

Drug Name
Fidarestat Drug Info
Synonyms
Aldos; FID; Fidaresstat; SK 860; Snk 860; Aldos (TN); SNK-860; Fidarestat (JAN/INN); (+)-(2S,4S)-6-Fluoro-2',5'-dioxospiro(chroman-4,4'-imidazolidine)-2-carboxamide; (+)-(2s,4s)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide; (2S,4S)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4'-IMIDAZOLIDINE]-2',5'-DIONE; (2S,4S)-6-Fluoro-2',5'-dioxospiro(3,4-dihydro-2H-1-benzopyran-4,4'-imidazolidine)-2-carboxamide; (2S,4S)-6-fluoro-2',5'-dioxospiro(chroman-4,4'-imidazolidine)-2-carboxamide; (2S,4S)-6-fluoro-2',5'-dioxospiro[2,3-dihydrochromene-4,4'-imidazolidine]-2-carboxamide
Indication
Disease Entry ICD 11 Status REF
Diabetic complication 5A2Y Phase 3 [1]
Cross-matching ID
PubChem CID
160024
CAS Number
CAS 136087-85-9
TTD Drug ID
DMZL1I8

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Aldose reductase (AKR1B1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Epalrestat DM5OGK0 Diabetic neuropathy 8C0Z Approved [4]
Sulindac DM2QHZU Acute myelogenous leukaemia 2A41 Approved [5]
Ranirestat DMD5QRS Diabetic neuropathy 8C0Z Phase 3 [6]
CONTIGOSIDE B DMX9V8K Thrombosis DB61-GB90 Phase 2/3 [7]
BNV-222 DMYFQJL Diabetic neuropathy 8C0Z Phase 2/3 [6]
BNV-222 DMYFQJL Diabetic neuropathy 8C0Z Phase 2/3 [8]
LIDORESTAT DMA0RI9 Diabetic complication 5A2Y Phase 2 [9]
QR-333 DMKVIWM Diabetic neuropathy 8C0Z Phase 2 [10]
ADMVA DM819CO Diabetic complication 5A2Y Phase 2 [6]
M-16209 DMZ7YX3 Diabetic complication 5A2Y Phase 2 [11]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Tyrosine-protein kinase JAK1 (JAK1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [12]
Quercetin DM3NC4M Obesity 5B81 Approved [13]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [14]
Isotretinoin DM4QTBN Acne vulgaris ED80 Approved [15]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [16]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [17]
Tofacitinib DMBS370 Rheumatoid arthritis FA20 Approved [18]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [19]
Clozapine DMFC71L Schizophrenia 6A20 Approved [20]
Zoledronate DMIXC7G Adenocarcinoma 2D40 Approved [21]
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Drug(s) Affected By Mitogen-activated protein kinase 3 (MAPK3)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [22]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [23]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [24]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [25]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [26]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [27]
Secobarbital DM14RF5 Epilepsy 8A60-8A68 Approved [28]
Gefitinib DM15F0X Colon adenocarcinoma Approved [29]
Fexofenadine DM17ONX Allergic rhinitis CA08.0 Approved [30]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [31]
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Drug(s) Affected By Mitogen-activated protein kinase 1 (MAPK1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ethanol DMDRQZU Chronic pain MG30 Approved [32]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [23]
Carvedilol DMHTEAO Chronic heart failure BD1Z Approved [33]
Paclitaxel DMLB81S Breast carcinoma Approved [34]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [35]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [22]
Urokinase DM0GOUD Myocardial infarction BA41-BA43 Approved [36]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [37]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [25]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [26]
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Drug(s) Affected By Interleukin-13 (IL13)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [38]
Prednisone DM2HG4X Acute asthma CA23 Approved [39]
Methotrexate DM2TEOL Anterior urethra cancer Approved [40]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [41]
Rifampicin DM5DSFZ Non-insulin dependent diabetes 5A11 Approved [42]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [43]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [19]
Budesonide DMJIBAW Allergic rhinitis CA08.0 Approved [44]
Alitretinoin DMME8LH Kaposi sarcoma 2B57 Approved [41]
Ethambutol DMR87LC Pulmonary tuberculosis 1B10.Z Approved [42]
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Drug(s) Affected By Signal transducer and activator of transcription 6 (STAT6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [37]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [45]
Methotrexate DM2TEOL Anterior urethra cancer Approved [46]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [41]
Panobinostat DM58WKG Chronic graft versus host disease Approved [47]
Marinol DM70IK5 Anorexia nervosa cachexia 6B80 Approved [48]
Ergotidine DM78IME Osteoarthritis FA00-FA05 Approved [45]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [19]
Ivermectin DMDBX5F Intestinal strongyloidiasis due to nematode parasite 1F6B Approved [49]
Temozolomide DMKECZD Adenocarcinoma 2D40 Approved [50]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Aldose reductase (AKR1B1) TTFBNVI ALDR_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Interleukin-13 (IL13) OTI4YS3Y IL13_HUMAN Protein Interaction/Cellular Processes [3]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [3]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [3]
Signal transducer and activator of transcription 6 (STAT6) OTCKMP49 STAT6_HUMAN Post-Translational Modifications [3]
Tyrosine-protein kinase JAK1 (JAK1) OT0X3D17 JAK1_HUMAN Post-Translational Modifications [3]

References

1 X-ray structure of the V301L aldo-keto reductase 1B10 complexed with NADP(+) and the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity. Chem Biol Interact. 2013 Feb 25;202(1-3):178-85.
2 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.
3 Aldose reductase inhibition prevents metaplasia of airway epithelial cells. PLoS One. 2010 Dec 28;5(12):e14440. doi: 10.1371/journal.pone.0014440.
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 Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8.
6 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).
7 Effect of Polygonum hydropiper sulfated flavonoids on lens aldose reductase and related enzymes. J Nat Prod. 1996 Apr;59(4):443-5.
8 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.
9 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.
10 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.
11 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.
12 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
13 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
14 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
15 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
16 Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF-kB signaling pathways synergistically. Clin Transl Med. 2021 Feb;11(2):e335. doi: 10.1002/ctm2.335.
17 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
18 JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. J Immunol Res. 2014;2014:283617. doi: 10.1155/2014/283617. Epub 2014 May 5.
19 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
20 Toxicoproteomics reveals an effect of clozapine on autophagy in human liver spheroids. Toxicol Mech Methods. 2023 Jun;33(5):401-410. doi: 10.1080/15376516.2022.2156005. Epub 2022 Dec 19.
21 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
22 Treatment with anticancer agents induces dysregulation of specific Wnt signaling pathways in human ovarian luteinized granulosa cells in vitro. Toxicol Sci. 2013 Nov;136(1):183-92. doi: 10.1093/toxsci/kft175. Epub 2013 Aug 16.
23 Progesterone increases csk homologous kinase in HMC-1560 human mast cells and reduces cell proliferation. J Cell Biochem. 2007 Dec 1;102(5):1271-80. doi: 10.1002/jcb.21357.
24 Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017 Aug 1;273:107-114. doi: 10.1016/j.cbi.2017.06.005. Epub 2017 Jun 7.
25 Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol Sci. 2014 Feb;137(2):404-15. doi: 10.1093/toxsci/kft254. Epub 2013 Nov 5.
26 Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2. Int J Cancer. 2006 Mar 15;118(6):1370-80. doi: 10.1002/ijc.21537.
27 Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell-matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis. Toxicol Appl Pharmacol. 2014 Mar 1;275(2):176-81. doi: 10.1016/j.taap.2014.01.005. Epub 2014 Jan 17.
28 Inhibition of activator protein 1 by barbiturates is mediated by differential effects on mitogen-activated protein kinases and the small G proteins ras and rac-1. J Pharmacol Exp Ther. 2004 Dec;311(3):1232-40. doi: 10.1124/jpet.104.071332. Epub 2004 Jul 19.
29 Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Res Treat. 2010 Feb;119(3):575-91. doi: 10.1007/s10549-009-0355-8. Epub 2009 Mar 15.
30 Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro. Int Arch Allergy Immunol. 2011;155(1):38-51. doi: 10.1159/000318720. Epub 2010 Nov 25.
31 SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxid Redox Signal. 2016 Feb 20;24(6):329-43. doi: 10.1089/ars.2015.6331. Epub 2015 Nov 10.
32 Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver. Toxicol Mech Methods. 2020 Jul;30(6):407-416. doi: 10.1080/15376516.2020.1747126. Epub 2020 Apr 1.
33 A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. doi: 10.1073/pnas.0707936104. Epub 2007 Oct 9.
34 The stent-eluting drugs sirolimus and paclitaxel suppress healing of the endothelium by induction of autophagy. Am J Pathol. 2009 Nov;175(5):2226-34.
35 Modulation of apoptosis in HaCaT keratinocytes via differential regulation of ERK signaling pathway by flavonoids. J Biol Chem. 2005 Sep 9;280(36):31498-507. doi: 10.1074/jbc.M505537200. Epub 2005 Jul 13.
36 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
37 Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
38 Benzyl isothiocyanate attenuates the hydrogen peroxide-induced interleukin-13 expression through glutathione S-transferase P induction in T lymphocytic leukemia cells. J Biochem Mol Toxicol. 2018 Jun;32(6):e22054.
39 Alterations in eotaxin, monocyte chemoattractant protein-4, interleukin-5, and interleukin-13 after systemic steroid treatment for nasal polyps. Otolaryngol Head Neck Surg. 2004 Nov;131(5):585-9. doi: 10.1016/j.otohns.2004.05.028.
40 Editor's Highlight: Modeling Compound-Induced Fibrogenesis In Vitro Using Three-Dimensional Bioprinted Human Liver Tissues. Toxicol Sci. 2016 Dec;154(2):354-367. doi: 10.1093/toxsci/kfw169. Epub 2016 Sep 7.
41 Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes. BMC Immunol. 2006 Nov 21;7:27. doi: 10.1186/1471-2172-7-27.
42 Detection of Drug-Responsive T-Lymphocytes in a Case of Fatal Antituberculosis Drug-Related Liver Injury. Chem Res Toxicol. 2016 Nov 21;29(11):1793-1795. doi: 10.1021/acs.chemrestox.6b00393. Epub 2016 Nov 9.
43 Inhibition of interleukin-13 gene expression in T cells through GATA-3 pathway by arsenic trioxide. Chin Med J (Engl). 2008 Nov 20;121(22):2346-9.
44 [Effects of beclomethasone dipropionate and budesonide on interleukin-13 induced cytokine release, proliferation and differentiation of the human lung fibroblasts]. Zhonghua Jie He He Hu Xi Za Zhi. 2007 Aug;30(8):599-604.
45 Pyrethroid insecticides influence the signal transduction in T helper lymphocytes from atopic and nonatopic subjects. Inflamm Res. 2003 Apr;52(4):154-63. doi: 10.1007/s000110300066.
46 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
47 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
48 Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells. Mol Pharmacol. 2006 Apr;69(4):1486-91. doi: 10.1124/mol.105.018325. Epub 2006 Jan 24.
49 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
50 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.