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

General Information of Drug (ID: DM31VE4)

• Drug Name: Sorbinil Drug Info
• Synonyms: SBI; Sorbinilo; Sorbinilum; Sorbinilo [Spanish]; Sorbinilum [Latin]; CP 45634; CP-45634; Sorbinil (USAN/INN); D-6-fluoro-spiro(chroman-4,4'-imidazolidine)-2',5'-dione; (4S)-6-fluoro-2,3-dihydro-2'H,5'H-spiro[chromene-4,4'-imidazolidine]-2',5'-dione; (4S)-6-fluorospiro[2,3-dihydrochromene-4,5'-imidazolidine]-2',4'-dione

Indication

Disease Entry	ICD 11	Status	REF
Diabetic cataract	9B10.21	Terminated	[1]

• Cross-matching ID:
  PubChem CID: 337359
  ChEBI ID: CHEBI:102029
  CAS Number: CAS 68367-52-2
  TTD Drug ID: DM31VE4

Molecule-Related Drug Atlas

Drug(s) Targeting Aldose reductase (AKR1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epalrestat	DM5OGK0	Diabetic neuropathy	8C0Z	Approved	[5]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[6]
Fidarestat	DMZL1I8	Diabetic complication	5A2Y	Phase 3	[7]
Ranirestat	DMD5QRS	Diabetic neuropathy	8C0Z	Phase 3	[8]
CONTIGOSIDE B	DMX9V8K	Thrombosis	DB61-GB90	Phase 2/3	[9]
BNV-222	DMYFQJL	Diabetic neuropathy	8C0Z	Phase 2/3	[8]
BNV-222	DMYFQJL	Diabetic neuropathy	8C0Z	Phase 2/3	[10]
LIDORESTAT	DMA0RI9	Diabetic complication	5A2Y	Phase 2	[11]
QR-333	DMKVIWM	Diabetic neuropathy	8C0Z	Phase 2	[12]
ADMVA	DM819CO	Diabetic complication	5A2Y	Phase 2	[8]

Drug(s) Affected By Aldo-keto reductase family 1 member B10 (AKR1B10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[13]
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[14]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[15]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[16]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[17]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[18]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[19]
Reserpine	DM6VM38	Hypertension	BA00-BA04	Approved	[20]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[21]
Disulfiram	DMCL2OK	Alcohol dependence	6C40.2	Approved	[22]

Drug(s) Affected By Aldo-keto reductase family 1 member B1 (AKR1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[15]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[23]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[25]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[26]
Disulfiram	DMCL2OK	Alcohol dependence	6C40.2	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[28]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[29]
Benzoic Acid	DMKB9FI	Alopecia areata	ED70.2	Approved	[22]

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	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aldo-keto reductase family 1 member B1 (AKR1B1)	OTRX72TH	ALDR_HUMAN	Gene/Protein Processing	[3]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Gene/Protein Processing	[4]

References

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• [2] A controlled trial of sorbinil, an aldose reductase inhibitor, in chronic painful diabetic neuropathy. Diabetes. 1983 Oct;32(10):938-42.
• [3] Aldose reductase inhibition suppresses airway inflammation. Chem Biol Interact. 2011 May 30;191(1-3):339-45. doi: 10.1016/j.cbi.2011.02.014. Epub 2011 Feb 18.
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• [5] 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.
• [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.
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• [16] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [17] Identification of approved drugs as potent inhibitors of pregnane X receptor activation with differential receptor interaction profiles. Arch Toxicol. 2018 Apr;92(4):1435-1451.
• [18] Characterization of drug-specific signaling between primary human hepatocytes and immune cells. Toxicol Sci. 2017 Jul 1;158(1):76-89.
• [19] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [20] Oxidative stress mechanisms do not discriminate between genotoxic and nongenotoxic liver carcinogens. Chem Res Toxicol. 2015 Aug 17;28(8):1636-46.
• [21] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [22] Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
• [23] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [24] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [25] Posttranslational glutathiolation of aldose reductase (AKR1B1): a possible mechanism of protein recovery from S-nitrosylation. Chem Biol Interact. 2009 Mar 16;178(1-3):250-8. doi: 10.1016/j.cbi.2008.11.007. Epub 2008 Nov 18.
• [26] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [27] 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.
• [28] 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.
• [29] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.